News this Week

Science  09 Jul 2010:
Vol. 329, Issue 5988, pp. 126
  1. U.S. Science Policy

    Panel Explores What It'll Take To Keep Universities Strong

    1. Jeffrey Mervis

    U.S. research universities may be the envy of the world, but they are under increasing stress. Endowments have shrunk, state support has declined, and operating costs are rising. University administrators say they also need help in complying with an increasing number of federal rules covering research topics that include bioweapons and financial conflicts of interest.

    Now, at the behest of Congress, the National Academies has convened a blue-ribbon committee to examine these concerns and recommend ways to keep research universities healthy. But universities are likely to be disappointed if they are hoping that the committee will conclude that money is the solution: “If we simply turn out a report that says, ‘Spend more money on research universities,’ we won't have done our job,” says the panel's chair, Charles “Chad” Holliday, retired CEO of DuPont.

    “I'm an industrial engineer. … And I haven't seen a system yet that can't be improved.”

    —CHARLES HOLLIDAY, PANEL CHAIR

    CREDIT: COURTESY OF BANK OF AMERICA

    Holliday, now chair of the board of Bank of America, said in an interview with Science that he intends to push the 21-member committee to take a close look at the way the universities themselves operate. “I'm an industrial engineer. We try to make systems work more efficiently. And I haven't seen a system yet that can't be improved,” says Holliday.

    “We know what a research university is supposed to do, and I don't think we're going to [recommend] changing that drastically,” he adds. “But if we could come up with different ways to accomplish that mission, I think it might be helpful.” The list of possible study topics, he says, includes everything from reducing the time to degree to making better use of new technology.

    The roots of the problem lie in an unwritten agreement between the academic community and the government that was struck after World War II. In return for receiving federal support for research, universities promised to create new knowledge that ultimately benefits society and to educate the next generation of scientists and engineers. But academic leaders say that historic partnership is fraying at both ends. “The quality of our research can only be as strong as the foundation upon which it rests,” Robert Berdahl, president of the Association of American Universities in Washington, D.C., explained last fall in a talk to the new committee's parent body, the Board on Higher Education and Workforce. “And if the fundamental operations of our research universities are deteriorating, the [country's] research superstructure will inevitably decline as well.”

    The university lobbyists who pushed for the new study took a page from an improbably influential 2006 academies' report on ways to strengthen the U.S. research enterprise that was requested by a bipartisan group of legislators with influence over science policy. That report, titled Rising Above the Gathering Storm, helped persuade Congress and the White House to embrace a 10-year doubling of federal spending on basic research, a goal enshrined in the 2007 America COMPETES Act.

    Similarly, the new committee grows out of a request 1 year ago by four legislators to the presidents of the three academies asking them to suggest the “top 10 actions that Congress, state governments, research universities, and others could take” so that U.S. research universities could continue to help the country “compete, prosper, and achieve national goals in health, energy, the environment, and global security.” Last month, after the Alfred P. Sloan Foundation put up most of the $1.5 million needed, the academies formally announced that the study was under way.

    The committee expects to meet for the first time in September and complete its work by next summer. Holliday is trying to speed up the process by talking with individual panel members before the initial meeting, for example, and using teleconferencing as much as possible. He hopes those strategies could be a model for other studies run by the academies' National Research Council.

    The Gathering Storm report actually made 20 recommendations in four areas, including for a massive boost in scholarships to train more science and math teachers and for changes to tax and immigration policies that would promote innovation. But its call for increased spending drowned out other proposals. Holliday, who was a member of that panel chaired by Norman Augustine, says that the new committee plans to revisit some of those issues that pertain to research universities. “Maybe we'll have the opportunity to make a more compelling argument the second time around,” he says.

    Asking universities to use existing resources in the most efficient manner is part of a larger trend, Holliday notes: “We're reducing the time it takes to do things across society, so the question is whether we are doing that in academia, too.” For example, he wonders, “Are there steps in the process [of earning a Ph.D.] that aren't adding value? If there's a way to speed up the process without sacrificing quality, it could ease the financial burden on students and also free up capacity to train more students.”

    Holliday says he understands the concerns surrounding unfunded mandates but only to a point. “My first reaction [to those complaints] is, ‘Join the club.’ I've been on the business side for 35 years, and that's how we feel, too.”

    Improving how universities work with industry to commercialize the fruits of academic research is another topic on the committee's plate. Holliday cites the position of “opportunity broker” that DuPont created when it moved into biotechnology—“someone who knew how to talk to leading-edge scientists in their labs and also the people who know how to apply their research to the market”—as a possible model. “My feeling is that research universities probably need the same sort of person,” he says.

    Holliday says his concerns about current academic practices don't undermine his conviction that “our research universities have got to remain strong.” Lawrence Summers, the former Harvard University president who is now director of the National Economic Council in the White House, agrees that the country's competitive edge derives in part from the “staying power” of its research universities. But universities should not rest on their laurels, Summers told Science. “At Harvard, I would often say that not having any failures would be the biggest failure of all,” he says. “Because it would mean that we didn't take enough chances.”

  2. Climate Monitoring

    Solar Sensor Grounded on Revamped Satellite Program

    1. Eli Kintisch

    U.S. climate scientists were hoping that the restructuring of a troubled $14 billion environmental satellites program would elevate the importance of climate sensors among instruments scheduled to fly over the next decade. But last week's announcement that the first spacecraft of the reconfigured National Polar-orbiting Operational Environmental Satellite System (NPOESS) wouldn't be able to measure the intensity of sunlight has left them feeling out in the cold again.

    “It's terrible news” that the Total and Spectral Irradiance Sensor (TSIS) has lost its ride to space, says solar physicist Judith Lean of the Naval Research Laboratory in Washington, D.C. Officials with NASA and the National Oceanic and Atmospheric Administration (NOAA) say they're committed to maintaining solar measurements, either by adding TSIS to future missions or dedicating one to it. In a tight budget environment, however, Lean says, “to not be a part of the satellite makes it more likely the sensors won't fly” anytime soon.

    The omission of TSIS flows from the Obama Administration's efforts to reform NPOESS. The massive weather and climate-monitoring program, under joint management by NASA, NOAA, and the Pentagon during the Bush Administration, has seen its cost double and its schedule fall 5 years behind since 2002 (Science, 5 February, p. 629). To reduce infighting and simplify the effort, the White House announced earlier this year that NPOESS would be broken into separate but cooperating components. NASA and NOAA would build and operate the Joint Polar Satellite System (JPSS), focused on weather and climate, while the Pentagon would build and run satellites aimed primarily at weather observations. The total number of satellites has yet to be decided.

    Flying free?

    Scientists are mulling a dedicated sun-monitoring mission similar to SORCE, launched in 2003.

    CREDIT: NASA

    Last week, NOAA announced that the first craft, JPSS-1, scheduled for 2014, will fly the same four sensors currently scheduled to go up next year on a preliminary mission known as NPP. That decision, which NOAA's Mary Kicza said is meant to “reduce risk” of future schedule or budget slips, leaves no room for TSIS, now under construction.

    That delay could cause a gap in the continuous record of solar brightness, crucial for calculating global warming, that has been maintained since 1978. The only current climate-relevant brightness sensor is on an orbiting NASA craft called SORCE, which is 5 years beyond its design life. A similar sensor is due to fly this fall on Glory. Because calibrating the sensors requires missions that overlap in time, however, scientists wanted TSIS to go up no later than 2014.

    TSIS program manager Tom Sparn, an engineer at the University of Colorado, Boulder, says the latest twist might actually be an opportunity. The original plan to keep TSIS focused on the sun while orbiting as part of a suite of instruments looking down at Earth requires hardware that adds vibration, increasing the engineering challenges and total cost. Sparn hopes that TSIS and other outward-facing sensors can fly on a dedicated solar JPSS solar platform. “We still have faith that in a timely fashion there will be a ride found” for TSIS, he says.

    Climate scientist Judith Curry of the Georgia Institute of Technology in Atlanta worries that the TSIS decision sends the wrong message about the state of climate monitoring in the latest configuration of environmental satellites. “We can probably survive in the interim without TSIS on JPSS,” she says. But “somebody somewhere needs to clean up this mess with NPOESS. Its new incarnation doesn't seem to be much better.”

  3. Genetics

    Volvox Genome Shows It Doesn't Take Much to Be Multicellular

    1. Elizabeth Pennisi

    How a single cell made the leap to a complex organism is one of life's great mysteries. Biologists have thought that new genes and gene networks would be needed to make possible the move to multicellularity. But, at least in green algae, that turns out not to be the case. On page 223, a comparison between the genomes of the 2000-cell Volvox carteri and a single-celled green alga, Chlamydomonas reinhardtii, has revealed surprisingly few differences in their gene makeup. “Even major evolutionary transitions can be accomplished via relatively subtle genetic changes,” says David Kirk, a developmental biologist at Washington University in St. Louis. As a result, solving this mystery “is going to take a lot more work.”

    Ever since the Dutch microbiologist Antonie van Leeuwenhoek discovered a multicellular Volvox in 1700, biologists have thought it would be a good model for studying how complex organisms arose. It belongs to a group that includes single-celled and multicellular species of varying degrees of complexity. Chlamydomonas reinhardtii, for example, is a single cell powered by two flagella that lives in soil and fresh water.

    Complex cousin.

    The juvenile Volvox (above), with its sphere of flagellated cells and 16 germ cells, is not much different genewise from the single-celled Chlamydomonas (left).

    CREDITS: S. PROCHNIK ET AL., SCIENCE

    By contrast, Volvox carteri, which is found in temporary and permanent ponds, has a much more complex life cycle. Adults consist of 2000 flagellated cells embedded in a spherical extracellular matrix, with 16 larger germ cells inside. Germ cells give rise to embryos in which dividing cells remain connected by cytoplasmic bridges from one cell interior to another, forming a hollow ball. At first all of the embryo's flagella face inward, but soon the newly formed embryo turns itself inside out, putting the flagella on the outside. Now called juveniles, these balls begin expanding by adding to their extracellular matrix and eventually burst out of the parental sphere. Soon after the juveniles leave the sphere, the rest of the cells die.

    In 2005, James Umen, a cell and developmental biologist at the Salk Institute for Biological Studies in San Diego, California, teamed up with Simon Prochnik and Daniel Rokhsar of the U.S. Department of Energy Joint Genome Institute (JGI) in Walnut Creek, California, and others to sequence the Volvox genome. JGI had already deciphered the genome of the single-celled Chlamydomonas.

    The 138-million-base Volvox genome proved to be 17% bigger than the Chlamydomonas genome, but not because of new genes. Instead, it contained more repetitive DNA, Prochnik, Umen, Rokhsar, and their colleagues report. Moreover, it has roughly the same number of genes—about 14,500—as Chlamydomonas. The researchers found few, if any, Volvox genes coding for novel proteins or protein subunits that could account for the difference in morphology between the two species. The gene networks that likely underlie the cytoplasmic bridges, the inversion of the sphere, and asymmetric cell division were quite similar in both species as well, says Umen.

    “It's surprising how few differences were found,” says Arthur Grossman, a plant biologist at the Carnegie Institution for Science in Stanford, California. “The findings suggest that it doesn't take very large changes in gene content to transition from a single-cell to a multicellular lifestyle.” He suspects that some genes have altered their function in Volvox to account for the changes, and he calls for a more in-depth look for small changes in gene—and protein—sequence.

    The findings parallel what Nicole King of the University of California, Berkeley, and her colleagues saw when they compared the genomes of a choanoflagellate—a close single-celled relative to animals—and several animals. The choanoflagellate had protein subunits, or domains, previously thought to be unique to metazoans, leading her to conclude that multicellularity in that part of the tree of life arose not so much from new genes but from a shuffling and recombining of existing genes and parts of genes.

    “What we found was even more similarities between the unicellular and multicellular organism,” says Umen. “The key transition is not inventing a whole bunch of genes and proteins; you just have to change the way you use what you have.”

  4. Polar Research

    Broken-Down Icebreakers Hamstring U.S. Science

    1. Jeffrey Mervis

    Biologist Carin Ashjian is hoping that her research cruise next winter will fill in some of the many blanks about how the Arctic ecosystem behaves during that forbidding season. But to do so, she'll need help from a good mechanic.

    Crunch time.

    Neither of the U.S. Coast Guard's two polar-class icebreakers, shown operating in Antarctica in 2002, are currently serviceable.

    CREDIT: PETER WEST/NATIONAL SCIENCE FOUNDATION

    That's how it works these days for scientists whose access to the polar regions depends on an over-the-hill and increasingly fragile U.S. icebreaking fleet. A 2006 report from the National Academies called for building two new icebreakers (Science, 6 October 2006, p. 33), but Congress has so far been unwilling to pony up the estimated $2 billion or more that would be needed to upgrade the fleet. The most that supporters have achieved to date is a Senate-backed call for a cost-benefit analysis of the nation's icebreaking needs.

    Such an analysis won't help Ashjian, a scientist at the Woods Hole Oceanographic Institution in Massachusetts. Her 6-week cruise aboard the Coast Guard cutter Polar Sea, the world's most powerful icebreaker, would be the first such scientific exploration of the Bering and Chukchi seas in January, Ashjian says. The goal is to provide information on water temperature, nutrient chemistry, and other biological and physical characteristics of this poorly understood ecosystem. “Right now, when we run our Arctic models, we don't know what to do with the winters because we know so little about what happens during that season,” she says.

    But the Polar Sea may not be available. In May, the 32-year-old ship limped into its home port of Seattle, Washington, after suffering engine trouble during a spring Arctic cruise. On 25 June, the Coast Guard announced that a 3-month scheduled maintenance had turned into a $3 million repair job that will stretch until “at least January 2011.” The Coast Guard has already canceled two fall events—one in support of a simulated oil spill in Arctic waters—and has told the National Science Foundation that the ship won't be able to provide backup support for the annual clearing of a winter passage through McMurdo Sound to the main U.S. research station in Antarctica.

    There's no other vessel in the U.S. icebreaking fleet that can do those jobs. The Polar Sea's older twin, the Polar Star, has been out of the water since 2006, and its $62 million “life extension” won't be finished until 2013. A third—and slightly younger—Coast Guard cutter, the Healy, is much less powerful, and a fourth, newer vessel operated by NSF, the Nathaniel B. Palmer, is a research ship with limited icebreaking capability. That thin bench is why NSF has relied in recent years on Swedish and Russian icebreakers to clear a passage to McMurdo (Science, 19 August 2005, p. 1164).

    Coast Guard officials have tried unsuccessfully to win approval for new polar icebreakers from both the Bush and Obama administrations. Legislators from maritime states aren't happy with the status quo. “On a national level, this eliminates the nation's only heavy icebreaking capability and seriously imperils our ability to respond to emergencies in ice-covered and ice-diminished waters,” said Senator Lisa Murkowski (R–AK), in response to the latest breakdown. “This could clearly impact our ability to preserve and protect U.S. interests in the Arctic.”

    A reauthorization bill now awaiting a House-Senate conference would require the Coast Guard to carry out a study by outside advisers “with extensive experience in the analysis of military procurements” of the cost of improving or adding to the fleet as well as the implications of not upgrading the nation's icebreaking capacity. “This subject's been studied to death,” says a Senate aide who follows the issue. “We'd like to see more, but right now it may be the best we can do.”

  5. ScienceInsider

    From the Science Policy Blog

    In the latest twist in a contentious debate about a possible tie between a retrovirus and chronic fatigue syndrome, the journal Retrovirology last week published a study that failed to find a key virus in blood samples from 51 CFS patients and 56 healthy people. The study, led by federal researchers, was held up in publication because it conflicts with another pending government study that confirms the connection.

    In what amounts to an unprecedented experiment, scientists are moving 700 turtle eggs from the beaches of Alabama and Western Florida to Florida's eastern shores. Protecting the creatures from the gulf oil spill is worth the risk that the embryos may be damaged or that the species' population genetics may be affected by the move, say scientists.

    For the second time, an investigatory panel at Pennsylvania State University has cleared climate scientist Michael Mann of charges of scientific malfeasance. The allegations had arisen after the release last year of hundreds of e-mails between climate scientists.

    In its first action on the 2011 budget for several science agencies, a House appropriations panel gave the National Science Foundation, NOAA, and NIST increases roughly matching the White House's request. But an unusually fuzzy budget picture could eventually render the numbers meaningless.

    A new report by the Massachusetts Institute of Technology calls for a variety of new research efforts to better exploit the large supply of natural gas in the United States.

    AAAS, which publishes Science, has condemned indictments issued by an Italian prosecutor against six scientists and a bureaucrat for failing to predict an earthquake that struck L'Aquila, Italy, in April 2009, calling them“unfair and naïve.”

    For more science policy news, visit news.sciencemag.org/scienceinsider.

  6. Biomedical Research

    Dream Team Plans a Blitz on Schizophrenia

    1. Jocelyn Kaiser

    BALTIMORE, MARYLAND—In a biotechnology park rising from razed rowhouses here, three top neuroscientists are betting big money and their scientific careers on a new approach to studying schizophrenia and other psychiatric diseases. With help from philanthropists, they are launching an institute that will look for treatments by probing early brain development for the origins of mental illness.

    Brains trust.

    Solomon Snyder (left), Daniel Weinberger, and Ronald McKay are launching an institute to study brain development and search for new schizophrenia drugs.

    CREDIT: RONALD MCKAY

    The nonprofit Lieber Institute for Brain Development will be led by Daniel Weinberger of the National Institute of Mental Health (NIMH), known for using brain imaging and genetics to study mental illnesses. Ronald McKay of the National Institute of Neurological Disorders and Stroke, whose lab was among the first to use stem cells to treat neurodegenerative diseases in animals, will be director of basic science. Both will leave government jobs for the new institute, which will be an independent affiliate of the adjacent Johns Hopkins University. The institute's third founder and elder statesman is Johns Hopkins neuropharmacologist Solomon Snyder, renowned for his work on brain receptors. Detailed responsibilities are still being worked out.

    The Lieber Institute's research agenda will include basic science and developing treatments for schizophrenia, a disease for which there have been few breakthroughs in the past 50 years. There are other centers dedicated to the brain, but they don't have the same develop mental focus, McKay says. “There's no other institute where these areas of science are brought together to solve the problem of mental illness,” Weinberger says.

    Financing comes from New York City investment banker Stephen A. Lieber and his wife, Connie. The Liebers have a daughter with schizophrenia and for more than 2 decades have led a major charity supporting research on mental illnesses. The couple say they have been struck by studies suggesting that the neural patterns that lead to schizophrenia are present at birth. About 6 years ago, they decided that this area needed “a Manhattan Project.” “We want to bring together a gifted group with a common trajectory aimed at finally seeing what happens in neurodevelopment that may lead to these disorders,” Stephen Lieber says.

    The Liebers talked to Yale, Columbia, and Rockefeller universities and the University of Pennsylvania before deciding to link up with Hopkins, largely because it agreed to allow the institute to be independent, Stephen Lieber says. (Lieber investigators will have appointments to the Johns Hopkins faculty.) Another incentive was the proximity of the National Institutes of Health (NIH), a 50-minute drive away.

    Start-up funding includes a $100 million commitment from the Liebers and $20 million from the Maltz Family Foundation in Cleveland, Ohio. There are plans to raise funds for an endowment, Weinberger says.

    The institute will begin with a $15 million budget and 30,000 square feet of space for labs. Weinberger expects to recruit 50 to 100 staff members within the next 5 years. Five initial projects will focus on stem cell biology, developmental neurobiology, neurogenetics, imaging, and a drug-discovery unit led by Snyder, who will remain on the Johns Hopkins faculty. McKay starts in late July in temporary space; NIMH neurologist Thomas Hyde will be acting director until Weinberger relocates a year from now.

    Another recruit is a prominent medical chemist from the pharmaceutical industry, which has been abandoning research on drugs for brain diseases, says Weinberger, who declined to name the researcher.

    Weinberger expects to have guest-researcher exchanges with NIH. He also hopes to partner with the agency to conduct early-phase clinical trials. Companies and universities could do that, but “they won't give up the intellectual property,” he says. The Lieber Institute's cell lines and data will be freely available, he says.

    The combined firepower of the three leaders, along with recent discoveries of genes that may underlie some cases of schizophrenia, give the institute a good chance at success, say researchers familiar with the Liebers' plans. “They're in the right place at the right time,” says psychiatrist Steven Paul, a former NIMH scientific director who recently retired as executive vice president for science and technology at Eli Lilly. “I don't think there are other institutes trying to do this in this holistic manner.”

    In an interview last week, the Lieber Institute's founders reflected on why they're giving up long-established programs for a new venture. The appeal: the freedom to pursue risky projects that's missing in grant-driven academia and opportunities to interact with industry that aren't possible at NIH. Showing off a vast, empty, glass-walled floor in a new building where their labs will soon take shape, Weinberger says launching the institute feels a lot like starting a biotech company. “But we have this wonderful opportunity not to be worried about profit,” he says.

  7. ScienceNOW.org

    From Science's Online Daily News Site

    CREDIT: RALPH STELZER

    Arctic Bees Still Need Their Beauty Sleep Even under the midnight sun, bees like their beauty sleep. Researchers have found that both native (Bombus pascuorum) and imported (B. terrestris) bumblebees in northern Finland, 270 kilometers north of the Arctic Circle, stuck to a regular workday, foraging local flowers from morning until evening and retiring to their nests at “night” despite the sun's 24-hour brightness. Working the graveyard shift would maximize their nests' food supply and boost their chances for survival. The results, published in the journal BMC Biology, suggest that, unlike reindeer and other Arctic creatures that lose their 24-hour biological rhythms in summer and winter, bees' internal clocks sync to cues other than light and darkness—perhaps variations in temperature or light quality—and that their nighttime rest confers an advantage even greater than extra food.

    Friendly Baboons Live Longer Want to live a long life? Have lots of friends. Studies in humans have made clear that people with stronger social networks have greater longevity. Now a new analysis shows the same is true for baboons.

    CREDIT: ANNE ENGH

    Joan Silk, an anthropologist at the University of California, Los Angeles, studied wild baboons in Botswana's Moremi Game Reserve, teaming up with a long-term project led by University of Pennsylvania biologist Dorothy Cheney and psychologist Robert Seyfarth. From 2001 to 2007, the researchers closely watched 44 female baboons, recording how often they approached each other, how long they groomed each other, and other measures of social interaction.

    Silk and colleagues reported in Current Biology that females who had the strongest, most stable, and longest-lasting relationships with other baboons lived significantly longer than those whose social ties were more fragile and unpredictable. Such findings in a nonhuman primate, the authors write, “suggest that the human motivation to form close and enduring bonds has a long evolutionary history.” The researchers speculate that friendship helps buffer the effects of stress and boost physiological repair mechanisms.

    Do Parasites Make You Dumber? Keeping your kids healthy might make them smarter, according to a new study that finds that countries most heavily affected by infectious diseases generally had the lowest average IQs.

    Some scientists have proposed that children who contract “parasites,” which includes everything from intestinal worms to bacteria and viruses, devote more energy to fighting off infection and thus have less energy available for brain development. As a result, countries where infectious diseases are prevalent will have lower intelligence, they argue.

    To test this idea, Christopher Eppig, a Ph.D. candidate in biology at the University of New Mexico, Albuquerque, and colleagues statistically analyzed the relationship between 2006 data on average IQs in different countries and 2004 data on infectious disease burden from the World Health Organization, which measures potential years of healthy life lost to premature death and illness. The researchers found that this burden was more closely correlated with average IQ than were other variables scientists have linked with IQ, they reported in the Proceedings of the Royal Society B. “Parasites alone account for 67% of the worldwide variation in intelligence,” Eppig says.

    While some scientists say opportunities for enrichment—which might be lacking in countries with low average IQ—are also needed for full brain development, others think Eppig's team, by concentrating on infectious diseases, is on the right track.

    Unexpected Downturn for Size of Proton Perhaps subatomic particles are feeling the pinch of the global recession, too: The highest precision measurement yet shows that the proton is 4% smaller in radius than previously thought. That's a big puzzle, as the theory used to calculate the quantity, quantum electrodynamics, is accurate to a few parts in 10 billion in other circumstances.

    CREDIT: WOLFGANG CHRISTIAN/DAVIDSON COLLEGE, HTTP://WEBPHYSICS.DAVIDSON.EDU/APPLETS/APPLETS.HTML

    Randolf Pohl of the Max Planck Institute for Quantum Optics in Garching, Germany, and 31 colleagues studied hydrogen atoms in which they replaced the electron that whizzes around the proton with a muon, a particle 207 times as heavy that decays in 2 microseconds. They then measured the relative shift in the energies of two of the atom's quantum states, or orbitals (right), caused by quantum fluctuations in the electric field binding the muon and the proton. That “Lamb shift” was bigger than expected, the team reports this week in Nature. The shift depends on the proton's radius, so the measurement suggests that the proton is smaller than indicated by similar experiments on ordinary hydrogen.

    Read the full postings, comments, and more at news.sciencemag.org/sciencenow.

  8. Epidemiology

    Will a Midsummer's Nightmare Return?

    1. Richard Stone

    In southwestern China, people of all ages have been dropping dead suddenly and inexplicably. After a 5-year pursuit, scientists have nabbed a surprising culprit.

    Unassuming.

    The first time Liu Jikai laid eyes on the small white mushrooms clustered on a tree stump, he didn't believe they could be toxic.

    CREDITS: COURTESY OF LIU JIKAI

    DALI, CHINA—Every summer, a killer stalks the rugged highlands of Yunnan Province in southwest China. Around the time the monsoon rains begin to fall in late June, “people grow afraid,” says Li Guanhui, the sole doctor in Wangjiacun, a village an hour east of the tourist town of Dali in northwestern Yunnan. Li, sitting on a stool in front of a snack shop, cracks a walnut with his bare hand and meticulously picks out the meat. After a while he looks up, brow furrowed. “We wonder,” he says, “who will be the first to die? Who will be next?”

    For more than 30 years, people of all ages have been dropping dead from sudden cardiac arrest in northern Yunnan. “It's getting everybody across the board: children, adults, older people,” says Robert Fontaine, an epidemiologist with the U.S. Centers for Disease Control and Prevention (CDC). The vast majority of deaths occur during the rainy season, from June to August. Yunnan Unknown Cause Sudden Death, as it is called, often strikes in clusters, so the first victim in a village instills dread in the rest of the inhabitants. “It's a fascinating problem,” says China's top expert on sudden deaths, cardiologist Zhang Shu of Fuwai Hospital in Beijing. Since 1978, more than 400 deaths and several dozen nonfatal cardiac cases have been attributed to the syndrome.

    But this summer, people across Yunnan may be able to rest easy. After a 5-year investigation, a team led by the Chinese CDC in Beijing believes it has uncovered the syndrome's chief cause. CDC and Yunnan Provincial Health Department have embarked on a campaign to warn against eating an innocuous-looking mushroom deemed so trifling that most villages don't even have a name for it. If they have fingered the real culprit—known for lack of a better description as the “little white mushroom”—then this summer could be the first in decades without a death from the syndrome.

    The case is not closed, however. Some researchers believe that a substantial percentage of syndrome deaths may be from another cause. Hoping to set lingering doubts to rest, the Chinese CDC–led team will test whether toxins isolated from the fungus, new to science, trigger the heart attacks. But they also acknowledge that some deaths remain unexplained and that other environmental factors may abet the little white scoundrel. “It's a long and complicated story,” says Chinese CDC epidemiologist Shi Guoqing.

    Portrait of a killer

    It dawned gradually on Yunnan health authorities that they had a problem on their hands. The unexplained deaths appear to have started in the late 1970s, largely out of sight in remote villages. As cases piled up, some experts began to suspect that the killer was Keshan disease, a rare heart malady linked to Coxsackie virus and low dietary intake of selenium, a trace element (Science, 12 June 2009, p. 1378).

    Hoping to cast a wider net, a team led by Huang Wen-li, deputy director of the Yunnan Institute of Endemic Diseases Control and Prevention in Dali, in 2002 compiled a long list of risk factors for the syndrome, including enterovirus infection, drinking water from mountain streams, abusing alcohol, and consuming vegetable oil and mushrooms. “But the evidence for any one factor was not convincing,” says Shi Wu-Xiang, an epidemiologist at Dali University who is not affiliated with the team. Two other commonalities were that the syndrome struck almost exclusively during the monsoon season, and in villages at altitudes ranging from 1800 to 2400 meters above sea level. A solution eluded the researchers, however, and the death toll mounted. In 2004, Huang and provincial authorities appealed to Beijing for help. The following spring, the science and health ministries held a conference on the syndrome. “There was a lot of political pressure to solve this mystery,” says Zeng Guang, Chinese CDC's top epidemiologist.

    The central government ordered the Chinese CDC to join the hunt. The task fell to its China Field Epidemiology Training Program (CFETP), an elite unit formed in 2001 with a mission to crack the toughest cases. The disease sleuths did not immediately warm to the idea of chasing a cardiac killer. Heart attacks are usually brought on by years of poor diet or lack of exercise. “Normally, I would not touch an investigation of sudden death with a barge pole. The deaths are usually from different causes, and the investigation will lead you nowhere,” says Fontaine, who is on assignment as senior adviser to CFETP.

    But the case was intriguing, so in June 2005, a team led by Zeng, CFETP's executive director, arrived in Dali and with Huang's group set up a surveillance system. Like clockwork, villagers started dying that July—and CFETP started assembling a vivid picture of their last moments. “We heard amazing stories about how people would drop dead in the middle of a conversation,” says Fuwai cardiologist Zhang Jian. But about two-thirds of victims, in the hours before death, experienced symptoms such as heart palpitations, nausea, dizziness, seizures, and fatigue—some of them hard to classify.

    At the time, Yunnan investigators were still leaning toward Keshan disease. Genuine Keshan cases had been recorded in areas that reported sudden deaths, and the region's soil is deficient in selenium. Promoting that idea were researchers from the Institute of Keshan Disease in Harbin who had collaborated with Huang's group. “They believed it was Keshan, so that's what they thought they were finding,” says Zeng. In August 2005, the government news channel CCTV aired a report on a hard-hit area, Jingdong County, which had tallied at least 40 sudden-death cases from 1993 to 2005. The TV program pinned the blame on Coxsackie virus.

    Shoe-leather epidemiology.

    After ruling out pathogens as the cause of the sudden deaths, Robert Fontaine (center, interviewing villagers) and colleagues at Chinese CDC realized they were on the trail of an unusual toxin.

    CREDIT: COURTESY OF CFETP

    That indictment quickly unraveled. Yunnan researchers had isolated Coxsackie virus from just four villages, and these were strains that are prevalent across China. There was nothing to suggest a new strain spreading, says Fontaine: “The overall pattern was totally inconsistent with Coxsackie virus.”

    The pathology was more revealing. In Keshan victims, Coxsackie virus ravages heart muscle, riddling the organ with lesions. Some hearts of sudden-death victims showed signs of mild infection, and some looked normal. “It's definitely not Keshan,” says Zhang Jian. About half the autopsies and tissue samples revealed severe underlying heart disease. Often the victims had signs of a genetic disorder called arrhythmogenic right ventricular cardiomyopathy, but that was not the answer either. The chronic condition develops slowly, and it's never been known to cause clusters, says Fontaine. Moreover, about two-thirds of cases within clusters were among people who were not related, making a genetic cause exceedingly unlikely.

    Lethal locale.

    The unexplained sudden deaths have occurred in northwest Yunnan.

    CREDIT: M.TWOMBLY/SCIENCE

    Then the team caught a lucky break: Local researchers that summer sent the Yunnan investigators pathology slides of heart tissue from three families in which two members of each family died at about the same time. The cardiac lesions were different in each member of each pair, Fontaine says. “And the pathologists said that none of it was enough to kill anybody,” he says, indicating that something like a drug or toxin was clearly throwing hearts off kilter. “All the evidence was pointing to a fatal arrhythmia.” To probe idea this further, the scientists sought to learn about the electrical activity of victims' hearts, as measured by electrocardiography (ECG). “We needed ECGs on these people before they died,” says Zhang Jian. The ECGs confirmed their suspicions.

    Reviewing all they had learned, the CFETP team kept circling back to the same suspect. “Mushrooms jumped out at us right away,” Fontaine says. But that didn't add up. Yunnan is famed for its wild mushrooms, including matsutake that end up on dinner plates in Japan and Boletus edulis, or porcini, that are shipped all the way to Europe. Villagers insisted they knew which are poisonous and which are edible. And it seemed that nobody else in the world was dying after dining on Yunnan mushrooms.

    Unlikely villain

    In the hills east of Dali, villagers lead a hard-scrabble life, says Shi Wu-Xiang, who over the past 5 years has assessed living standards in places where the syndrome has struck, including Wangjiacun. “This disease is related to poverty” and perhaps influenced by local customs, he says. Mushrooms are a key part of everyone's life. On average, Shi says, one-third of villagers' income is from tobacco farming, one-third is from other crops such as rice and from handcrafts, and one-third is from wild mushrooms.

    Mushrooms are gathered in July and August—the height of the rainy season. “Almost the entire village collects,” says Li Linmei, a farmer in Wangjiacun bedecked in pale-green bracelets made of local jade, a talisman thought to promote longevity. Families fan out into the countryside, she explains, and will often spend several nights at the mushroom grounds. “Mushroom ladies” go village to village buying up the bounty and moving it to middlemen who sell to restaurants or exporters.

    Mushroom picking could explain the syndrome's seasonality and narrow altitude band, says Shi Guoqing. Soon after arriving in Yunnan in 2005, his group had queried villagers about fungi. “We had no idea what kind of mushroom we were looking for. So we asked them what kind they ate,” he says. Most villagers, they learned, refrained from eating mushrooms. “They are very poor; they want to earn money. So they don't eat the fat and juicy ones; they sell them,” Shi says.

    But then in 2006, CFETP began chasing an important new lead. That year, they found curious mushrooms in one home that had experienced sudden deaths. Then a sudden death occurred in another county—and the victim's family members admitted that they had consumed this kind of mushroom. “The mushroom ladies never buy them,” Shi says. These mushrooms, little and white and fragile-looking, have no commercial value and turn brown quickly after being picked. The CFETP team learned that 3 years earlier, Huang's group, while investigating a case cluster, had collected the nameless mushroom, diced it, and fed it to mice. The animals suffered no ill effects, so the experiment was filed away as a negative result. Dubious, Chinese CDC toxicologists brought samples back to Beijing and did their own mouse-feeding study. They too did not observe an effect.

    But in 2007, the circumstantial case against Little White grew stronger. The CFETP team heard about two more sudden-death clusters and raced to the villages. They showed photos of the mushroom to surviving family members and neighbors, who confirmed that the stricken individuals had eaten it. Could the toxicology tests have been misleading? they wondered. “We thought the mushroom might contain a low-level poison,” Shi says. “Some people may eat this, no problem. Other people who eat too much, or who have underlying heart disease—they may have trouble.” The mice might not have consumed enough of the fresh mushroom to show an effect, Shi says. They had to try again.

    Going door to door.

    Epidemiologist Shi Wu-Xiang (left) queries a farmer in Wangjiacun about his plans for gathering wild mushrooms this summer. Most villagers can only afford to eat mushrooms that they are unable to sell.

    CREDIT: R. STONE/SCIENCE

    The next summer, CFETP asked Liu Jikai, a medicinal chemist at the Kunming Institute of Botany, in Yunnan's capital, to make preparations of the suspicious mushroom for toxicity testing. Liu had recently extracted several antitumor agents from Yunnan mushrooms, including what may be the priciest variety in all of China: ganbajun, or groundwart, which can cost up to $100 per kilogram. From that species, his group has identified eight new pigments that are 20 times as potent antioxidants as vitamin E.

    The first time Liu laid eyes on Little White, “I didn't believe it could be toxic,” he says. His institute colleague, taxonomist Yang Zhuliang, deduced that the mushroom is a new kind of Trogia. “Not much is known about this genus,” Liu says, apart from the fact that it was not thought to include poisonous species. Little White, which sprouts from downed trees, was by no means rare. Yet numerous surveys had missed it.

    In 2008, the Institute of Laboratory Animal Science in Beijing tested Liu's extracts in mice—and all the animals died. With evidence mounting against Little White, CFETP and local health officials began to warn villages to steer clear of it. Shi Guoqing's team went to Jingdong, the blighted county in the CCTV program. Earlier, local investigators had not found the mushroom there. But when CFETP staff showed pictures to villagers, Shi says, “they said, ‘Yes, we ate this, but we thought it was safe.’”

    Last year, 15 of 16 sudden deaths blamed on the syndrome occurred in areas with no previously reported cases, including 14 in one county. These areas had not been alerted to Little White. Among the deaths were four members of a family: the mother, two daughters, and a son-in-law. Two young children survived. “They could not tell us anything useful,” says CFETP's Shen Tao. “But we found dried little white mushrooms in the kitchen. It was quite clear what had happened.”

    In the meantime, scientists and an army of farmers hit the highlands last summer and “collected a huge amount” of Little White, Liu says. In the months since, his group has attempted to unmask the toxin. First, they zeroed in on ammonia-based cyclic peptides. These proved benign. Then they isolated three unusual amino acids. Most amino acids are building blocks of proteins, but Little White's trio is not associated with any protein, and one is new to science. “All three are toxic but not extremely so,” says Liu. Dissections of mice infused with the amino acids revealed intestinal bleeding and edema—but no cardiac lesions. That makes sense, says Fontaine. “If you find a lesion in the heart, then you've got the wrong poison,” he says, because human victims also don't have cardiac lesions from the toxin.

    The mechanism remains a riddle. “What's happening in Yunnan isn't expected from any other mushroom toxin,” says Fontaine. “What we have here is a toxin that's picking off vulnerable people. Anybody who is susceptible and is pushed over the edge will get a fatal arrhythmia.”

    An accomplice—or second killer?

    Not everybody buys that explanation. “I don't think it's related to mushrooms,” says Wangjiacun's doctor, Li Guanhui. He believes that mountain streams are contaminated with a toxin or pathogen that causes the syndrome. In his experience, he says, “most cases are linked to dirty water.” Fuwai's Zhang Jian sees merit in that idea. “People in that area like to drink water from the mountain,” he says. “To me it has a very strange taste, but villagers don't like to drink purified water because it has no taste!” His Fuwai colleague Zhang Shu also is not convinced that the little white mushroom is the sole culprit. “I don't think this is the last word,” he says.

    Indeed, not all sudden-death victims ate the mushroom. But CFTEP researchers think they have the explanation. From the start of the investigation, they had suspected that heavy metal poisoning may play a role in the syndrome. One element seemed most likely: barium, which is used to induce arrhythmias. “If you want to test a drug for antiarrhythmic properties, you give lab animals barium,” Fontaine says.

    In 2006, the team rushed to two villages that had reported sudden-death clusters and took blood samples from victims and surviving family members. Many had high barium levels; one victim's was highest. Two years later, examining another cluster, they measured high barium levels in the blood, urine, and hair of victims, as well as in local water. In some Yunnan mushrooms—including Little White—barium readings were off the chart. Also pointing to barium are dozens of ECG readings of ill and healthy villagers. A remarkable 40% of exams revealed an abnormal heart electrical pattern called a long QT interval, a major risk factor for sudden death. Barium is known to trigger a long QT.

    Putting the strands together, Zeng's team hypothesizes that the little white mushrooms have caused a large share of sudden deaths in Yunnan, perhaps abetted by barium from local foods or untreated water. If a sudden death occurs this year, CFETP researchers hope to detect Little White's amino acids along with barium in the victim's blood. “That would be strong direct evidence,” Liu says.

    One question may never be answered. “It's still a puzzle why the villagers didn't figure out themselves that the mushrooms are toxic,” Fontaine says. But as a public health threat, he says, Yunnan sudden death syndrome may have been vanquished.

  9. Scientific Collections

    The Legacy Plan

    1. Jennifer Couzin-Frankel

    After a long career, you're ready to close the lab and give away a lifetime's worth of specimens. Who will take them?

    Nobel-sized attic.

    Baruch Blumberg has hepatitis B virus samples going back 50 years.

    CREDITS: J. COUZIN-FRANKEL/SCIENCE

    PHILADELPHIA, PENNSYLVANIA—He never studied history, but Baruch Blumberg is surrounded by it. His home in downtown Philadelphia is steps from an 18th century graveyard that he cuts through to reach the local coffee shop. He presides over the American Philosophical Society, founded by Benjamin Franklin, who, as it happened, died “right down the street,” Blumberg says. The walls of his top-floor office are lined with mementos of his nearly 85 years: photos from his time in the U.S. Navy, a certificate marking his induction in 1993 into the National Inventors Hall of Fame, a black-and-white photo of a long-ago field trip to Africa. He even has what appears to be an autographed photo of Albert Einstein that reads, “Congratulations Barry, Al.”

    “Impressive, eh?” says Blumberg, before confessing that the picture is actually from Life magazine, one he tore out and signed himself back in grade school. And saved.

    Blumberg has other trophies. Among the most valuable, in his estimation, are those that helped him win a Nobel Prize in 1976 for discovering the hepatitis B virus and inventing a vaccine against it. During the decades he spent studying the liver disease, he collected more than 450,000 blood samples. Although Blumberg remains active, his lab at Philadelphia's Fox Chase Cancer Center closed years ago and his sample collection sits mostly unused, with an uncertain future. No one seems to know quite what to do with it, least of all Blumberg himself.

    Scientists don't like to stop working. Yet eventually, at least some do move on and bid their colleagues farewell. And then their collections of blood, DNA, cancer tissue, and more, amassed over the course of their career, need a new steward. But finding one can be difficult, given the cost of archiving and storing samples, as well as concerns about their quality and the suitability of informed consent obtained long ago.

    “These samples—they're not easy to separate yourself from,” says Anna O'Connell, who retired in February after 51 years at Fox Chase. She spent 40 of those years managing Blumberg's hoard, which eventually took up three and a half giant walk-in freezers, each one measuring 3 meters by 3 meters. For researchers, “it's like their lives are there,” O'Connell continues. They've dedicated themselves to the samples, and the samples have helped fuel their career. “But sometimes,” says O'Connell, “you have to make a decision” to let go.

    There is no academic standard to guide collection bequests, no national repository to hold them. Current studies often include central banks for tissue and DNA, but many researchers, particularly those nearing retirement age, still keep personal repositories in their lab freezers. There's pressure on them to develop contingency plans, but few are willing to confront the toughest issue: whether their collections, which they hold dear, are worth preserving indefinitely.

    Winding down

    “We've got an aging workforce,” says Carolyn Compton, who heads the Office of Biorepositories and Biospecimen Research at the National Cancer Institute (NCI) in Bethesda, Maryland. She knows more than she would like about retiring researchers hunting for a place to stash their samples. “Investigators send these heart-rending pleas to the NCI,” begging the institute to “take over these collections. … I can't tell you how common this is.” Compton has little sympathy for them. “The NCI has no budget for funding your biospecimen collection for all eternity.”

    In the last month or so, Compton has had two requests from retiring researchers who amassed large biorepositories and want NCI to adopt them. The answer was the same she gives to all such inquiries: Sorry, but no.

    “The NCI has no budget for funding your biospecimen collection for all eternity.”

    —CAROLYN COMPTON, NATIONAL CANCER INSTITUTE

    CREDIT: NATIONAL CANCER INSTITUE

    Because tumor tissue is so often banked for research after surgery, NCI struggles with storage more than most. For years, it offered little guidance. Then in 2007, NCI released its “best practices” for biospecimens, urging researchers to develop what Compton calls a “legacy plan.” Essentially, she's talking about a will spelling out the fate of specimens if funding evaporates, the study for which they were collected ends, or the researcher holding them retires or dies.

    Unlike a traditional will, the options for specimens are more limited and potentially much more complicated, because the decision isn't the researcher's alone. In a landmark court case in 2006, a Missouri judge ruled that specimens don't belong to the researcher but rather to the institution. The case of Washington University v. Catalona pitted the St. Louis school against a prostate cancer specialist, William Catalona, who was moving to Northwestern University in Chicago, Illinois, and wanted to take his vast repository with him. The judge ruled in favor of Washington University, which sought to keep a potentially lucrative blood and tissue bank—a decision upheld the following year on appeal (Science, 29 June 2007, p. 1829).

    Human samples come with myriad other issues. Samples collected before the mid-1990s tend to have less stringent terms of informed consent. “Individual consent was not considered necessary” decades ago, Blumberg recalls, when he visited remote communities worldwide—in Africa, South America, the Arctic, the Pacific Islands, and elsewhere. Permission from village leaders and local medical personnel was enough.

    Researchers rarely try to predict what future generations will demand of their samples. “It's not something you think about when you're 35 and starting your career,” says Kenneth Kidd, a geneticist at Yale University who with his wife, Judith, a physical anthropologist, has amassed 3000 samples from 57 different populations. The Kidds, both 69, developed health problems several years ago. Although now both are doing well and are hard at work, the experience prompted them to consider for the first time the future of a collection they deem both rare and valuable. “We realized that we were not immortal,” Kidd says.

    Dream on.

    Long-term storage in liquid nitrogen, used at the Coriell Institute for Medical Research repository, is not always an option for old collections.

    CREDIT: CORIELL INSTITUTE FOR MEDICAL RESEARCH (2)

    The Kidds have strong feeling about how their samples ought to be used by others—or more precisely, not used. Consent forms for samples collected beginning in the 1990s state that they cannot be sold or otherwise generate a profit or patents, and “we are imposing the consent retroactively” on older samples that lacked this clause, because no one considered it at the time, says Kidd. “We realize that if we went to the same population today, they would want that.”

    Whereas the Kidds are narrowing consent, donors today often give much broader consent than in the past. Samples can be shipped anywhere, for example, or used to study any number of diseases. “The consent [from the past] might preclude you from doing anything, even though you know you have a gold mine in the freezer.” says Anna Suk-Fong Lok, a liver disease specialist at the University of Michigan, Ann Arbor.

    Quality control and accurate record-keeping are critical, too. Samples might be degraded from having been frozen and thawed many times, or data describing them might have been marked on “sheets of paper that no one else can find,” says Lok. Even with good consent, she says, she'd need to know whether the samples are in usable condition and come with reliable clinical information—in other words, if “you don't even know whether sample 1 and sample 101 belong to the same person, then there's really nothing you can learn.” Although Lok says Blumberg's collection might be of benefit to her, “I would ask him all these questions” before agreeing to take on any samples.

    Golden opportunities

    Despite their limitations, decades-old specimens can yield unexpected treasures.

    Leonard Seeff, like Blumberg a hepatitis specialist, was making his “liver rounds” at the Walter Reed Army Medical Center in Washington, D.C., back in the 1990s when he overheard a colleague talking about nearly 100,000 blood samples he had recently acquired. “They had been drawn on an air force base in Wyoming” between 1948 and 1954, says Seeff, now 74 and a part-time scientist at the U.S. Food and Drug Administration. “They sat in a basement for 25, 30 years” at least, he says. After the researcher who collected them died, the hospital stacked them in an ice cream truck and sent them to an infectious-disease specialist in Minneapolis, Minnesota, who was willing to take them on. Legend had it that the basement freezers in which they'd been stored were themselves encased in ice, because they sat underneath a leaky air conditioner—meaning the samples were better preserved than one might expect.

    Seeff immediately saw an opportunity. He had more than 8000 blood samples tested for hepatitis C, whose origins were uncertain, and found that a handful contained the virus—the earliest it had been detected in the United States. Furthermore, he and some colleagues managed to track down six members of the group who had been infected, and “most of them were doing fine some 45 years later”—providing valuable information on the natural course of the disease. Old samples can answer questions that others cannot, and some argue that this makes them worth preserving.

    Sitting in his shaded garden on a muggy day, wearing khakis and sandals, Blumberg describes the huge reel-to-reel tapes that hold data on his earliest samples. (Data on newer ones are stored in a secure computer system.) He believes the specimens, which are stripped of names, could be useful in the hunt for new viruses or other microorganisms, or to track the evolving history of hepatitis B and other genomic sequences. The oldest date from 1957, he says. Among other things, he used samples collected from leprosy patients in the Democratic Republic of the Congo to determine that those chronically infected by the retrovirus HTLV-1 were much less likely to survive than were patients who were uninfected.

    When it comes to informed consent, says Blumberg, “I haven't looked into it. … One would have to consider each collection independently,” for example, those that made up distinct studies. O'Connell says that although any new research project on the samples would need careful vetting, the consent under which they were collected was “always broad” and they can be used for anything.

    Virus and vaccine.

    Blumberg's hepatitis samples were the basis of lifesaving discoveries.

    CREDITS: WIKIPEDIA; MICHELLE DEL GUERCIO/PHOTO RESEARCHERS INC. (INSET)

    But even when samples are in good condition, no one else might care as much about them as the person who lovingly collected them. In 2003, Kirsten Fischer Lindahl retired from the University of Texas Southwestern Medical Center at Dallas, where she had worked in mouse genetics. Like almost everyone else, she didn't give much thought to what to do with her vast repository of mouse tissues until she was on her way out the door—and then she started to worry. The Howard Hughes Medical Institute, which had supported Fischer Lindahl's research, offered her a liquid-nitrogen storage tank until she sorted out what to do with the samples.

    Four months after she left, the tank malfunctioned. “The whole thing thawed and it had to be thrown out,” she recalls. At the time “it seemed terrible.” But soon she felt a weight lifted off her shoulders. In retrospect, she says, no one, other than her, was inclined to parse the mouse tissue. In 7 years, she's gotten maybe two requests for the samples.

    Although not retired, Lok experienced something similar when she relocated from Hong Kong to the United States. Her university in Hong Kong exerted its right to keep hepatitis samples she'd collected, so Lok divvied up each blood specimen, taking half for herself and leaving half behind. “No one ever touched the samples” in Hong Kong, she says. Meanwhile, “I published 22 papers based on them.”

    History in vials

    Most of Blumberg's samples sit in an old attic on Fox Chase's leafy campus. To reach them, one takes an elevator two stories and then climbs a flight of stairs, with the outdoor heat seeping in. The attic used to house library stacks; now, three massive walk-in freezers take up nearly all the space. They're kept at or below -20°C, and lined with hundreds of boxes filled with vials of serum. Each box is hand-numbered and sometimes labeled with the vials' population of origin: Finnish, Mexican Indians. At the top left of one freezer sits box 0001: the very first samples Blumberg collected.

    Two years ago, more than 40,000 of Blumberg's more recent samples were shipped to the Hepatitis B Foundation in Doylestown, Pennsylvania, for research projects. Now, Fox Chase is likely to take them back. O'Connell thinks the cancer center ought to consider investing in more modern “uprights” for storage—but those cost $8000 to $10,000 each, and Blumberg's collection would occupy 10 of them.

    Blumberg believes it would take an archivist 2 to 3 years to sort through his collection to determine the samples' condition. “Some may have evaporated,” he says. In the end, an archivist “may decide they're not valuable,” although, he says, “I think a lot of them are.” Destroying even some of the samples troubles him. “We're sort of stewards of this information that could be used in the future.”

    Jonathan Chernoff, deputy scientific director at Fox Chase, has been talking with O'Connell and Blumberg about what to do. “I don't think I'm smart enough” to anticipate how the collection could serve science in the future, says Chernoff. He poked around to determine whether the samples were still being used, and the answer was, not often. Ironically, Blumberg's success in developing the vaccine has made his own collection obsolete—at least for hepatitis B work, where, says Chernoff, “the science has moved on” and, although there are still new infections each year, relatively few people work in the area. On the other hand, the samples might come in handy for other projects. “It could be that a few years from now someone could say, ‘If only I had samples from Senegal from the '60s and '70s’” to answer a particularly pressing research question, Chernoff points out. “I hate to be the guy to say, ‘Well, we used to have those until we threw them out.’”

    Given the uncertainty, Chernoff plans to keep the samples at Fox Chase while he's in his current position. But in the long term? “I don't know that I can convince another generation to hold on to these as memory fades,” he says. Like Blumberg, Chernoff wishes there were dedicated funding, or a national archive, for historic specimens like these.

    Going forward, research institutions are considering their options. The Medical Research Council in the United Kingdom is setting up the UK Brain Banks Network to ensure that samples are carefully preserved and widely available for research. Many universities and cancer centers, including Fox Chase, are establishing their own repositories with consistent standards. One long-term solution for cancer research could lie in “a Match.com for specimens,” says Compton. With echoes of the popular dating site, a Web tool called the NCI Specimen Resource Locator matches specimens in need of a home with researchers willing to take them in.

    Still, hundreds of investigators maintain personal collections. And, says Compton, they don't think about them “with this kind of seriousness of intent. Their idea of a biorepository … is a freezer in the hallway with an Excel spreadsheet taped to the door.” For those, a legacy plan comes only when someone realizes it's missing.

  10. Profile: John Rogers

    Farewell to Flatland

    1. Robert F. Service

    By creating electronic materials that bend and stretch, a pioneering researcher could change the way we light our homes, treat diseases, and power the planet.

    CREDIT: THOMPSON-MCCLELLAN

    In the summer of 2000, at age 33, John Rogers was named as one of the youngest department managers ever at the famed invention shop, Bell Laboratories in Murray Hill, New Jersey. But within months, he was caught in the middle of what he calls “a complete disaster.” Shortly after Rogers took the helm of his department, a Bell Labs postdoc and physicist named Jan Hendrik Schön joined the lab's full-time staff. Schön was already a hotshot at Bell Labs and beyond. In a series of high-profile papers, Schön and Bell Labs colleagues reported a steady stream of advances illuminating the way electric charges move through organic crystals. They saw superconductivity, the fractional quantum Hall effect, laserlike behavior—each advance more dramatic than the last. Conference invitations poured in. There were even rumors of a possible Nobel Prize.

    Then it all came crashing down. In the autumn of 2002, Schön was found to have faked experimental results in at least 17 published papers (including six in Science). “It was off-the-charts awful,” Rogers recalls. “I hadn't managed a postdoc before, much less a department, much less a monster.” His anger over what he considers Schön's betrayal remains fresh.

    To make matters worse, Lucent Technologies—then Bell's parent company—was in the process of imploding financially, forcing managers to shed staff members and talent. Rogers says that at the time he wasn't overly concerned that Schön's misdeeds would contaminate him. “I was more concerned about the taint on the lab. It didn't affect Lucent's decisions [to cut research staff members]. But it didn't help.”

    Shortly after news of the fraud broke in the summer of 2002, Bell Labs investigated and ultimately fired Schön (Science, 4 October 2002, p. 30). And in December 2002, Rogers left Bell Labs to take an academic position at the University of Illinois, Urbana-Champaign, in hopes of giving his career a fresh start.

    Rogers hasn't just survived—he has thrived. Running a lab with some 40 students and postdocs and working with colleagues and collaborators around the world, Rogers has pioneered a new approach to patterning conventional flat, rigid semiconductors, such as silicon, atop lightweight, flexible surfaces of nearly any type and shape. That advance is ushering in a new era of lighting, medical equipment, and solar cells that are all quickly moving to commercialization and garnering Rogers plenty of attention. Last fall, Rogers won a MacArthur Fellowship, commonly called a genius grant. And others are offering praise as well. “I've been a fan of John's from the beginning,” says Michael McAlpine, a chemist at Princeton University, who also works on novel flexible electronic devices. “He's one of the most creative scientists out there.”

    Science that works

    Rogers's knack for finding novel ways to manipulate semiconductors started early. After earning degrees at the University of Texas, Austin, and the Massachusetts Institute of Technology (MIT), Rogers served as a postdoc with George Whitesides, a chemist at Harvard University. Whitesides, a Renaissance scientist with expertise in fields as far-ranging as nanotechnology and the origins of life, was looking for a cheaper alternative to photolithography, the technique used to pattern computer chips. Rogers helped develop a technique called microcontact printing, capable of patterning tiny features using what amounts to advanced rubber-stamping techniques.

    While working at Harvard, Rogers also formed a start-up company to commercialize his doctoral work at MIT: a technique for measuring the thickness of metal films with lasers, still used by chipmakers today. Although commercializing a new technology was difficult, Rogers says that seeing his work succeed commercially gave him a taste not just for pushing scientific boundaries but for inventing technology that affects people's lives. After Harvard, Rogers jumped to Bell Labs, where his approach of coupling science and engineering was strongly encouraged. The company had a reputation for backing revolutionary basic research. But with Lucent struggling, managers were desperate to provide potential products for its business units. Rogers came up with a technique for designing miniature heaters on the surfaces of optical fibers to control the way light propagates through them. The technology quickly moved into products and, like the laser thickness meter, is still sold today.

    The ordeal with Schön barely dented Rogers's personal success at Bell, but Rogers says the experience left its mark on his approach to science. “It probably under-scored my emphasis on engineering,” he says. “If you are making a physical thing and send it to a collaborator, it has to work in other people's hands. It takes the issue of fraud off the table.”

    Stretchy circuits, bright tattoos

    The novel stamping techniques Rogers developed with Whitesides proved ideal for patterning the newly popular flexible organic electronics. Rogers himself developed a love-hate relationship with the materials. Their malleability made them ideal for many novel applications, such as lightweight or curved displays. But electrical charges plod through organics, making organic electronics slow. Rogers wanted the best of both worlds: the speed, light-emitting capabilities, and durability of inorganics, and the flexibility of organics.

    He found it by turning to nanotechnology. In a series of papers starting in 2005, Rogers and colleagues showed that most flat, rigid, high-performance semiconductors could become flexible if they were merely cut into ribbons just a few tens of nanometers thick. A paper published online in Science on 15 December 2005, for example, described a way to pattern silicon nanoribbons on rubber sheets so that the ribbons not only bent when flexed but continued to function as semiconductors. Rogers's team went on to make ever-more-sophisticated designs, including novel ways of making bendable circuitry, solar cells, and lights. Although not alone in this pursuit, “Rogers has been a pioneer in this direction,” says Ali Javey, an electrical engineer at the University of California, Berkeley.

    New twist.

    Flexible devices for monitoring brain activity (left) and making cheap solar power (right).

    CREDIT (LEFT TO RIGHT): D-H. KIM ET AL., NATURE MATERIALS 9, (18 APRIL 2010) ©2010 NATURE PUBLISHING GROUP; J. YOON ET AL., NATURE 465, (20 MAY 2010) ©2010 NATURE PUBLISHING GROUP

    More recently, Rogers and his colleagues have begun showing off what they can do with flexible electronics. In a paper published online in Science on 27 March 2008, for example, they reported that their printing techniques could make silicon circuitry that not only bends but even folds. Down the road, such pliable circuits could be useful for making paperlike displays that can be folded, or biomedical devices that flex like skin to conform to a person's body.

    Such complex devices are a major focus for the Rogers group, says Zhenan Bao, a former colleague of Rogers's at Bell Labs, now a chemist specializing in flexible electronics at Stanford University in Palo Alto, California. “In a lot of his projects, you see not just a single transistor or single solar cell but an array or a medical device,” Bao says. “It allows you to start imagining what future technology will look like.”

    Another recent push for Rogers has been in solar cells. Organic solar cells typically transfer only 5% to 10% of the energy in photons into the electrons that make up an electric current. Silicon does far better, about 20%. Compound semiconductors such as gallium arsenide (GaAs) can top 40%, which is why they are used for generating power in space. But GaAs is very expensive.

    Rogers, his Illinois colleague Ralph Nuzzo, and others reported in the 20 May issue of Nature a way to make cheap GaAs solar cells by printing tiny flecks of the material on plastic. Starting with an expensive GaAs substrate, they use conventional semiconductor growth techniques to grow stacks of two alternating semiconductor alloys on top of it. The first is the material from which the solar cells will be grown, a combination of GaAs and aluminum gallium arsenide (AlGaAs). The second is a “sacrificial layer” made from a different semiconductor alloy. The researchers cut a grid of lines through these alternating layers and then chemically etch away all the sacrificial layers at once, liberating thousands of flecks of high-quality GaAs/AlGaAs. The GaAs substrate is reused to make a new batch of flecks. Finally, they use their stamping techniques to print the flecks in a regular array on a plastic sheet. The flecks are wired up and topped with glass lenses. The lenses capture light over a large area and focus it on the tiny semiconductor flecks, which convert the light into electricity.

    “John has done great work—not only beautiful science, but he takes an approach that can be transitioned to industry,” Javey says of the new work. The transition is already taking place. Rogers, Nuzzo, and others recently licensed their GaAs technology to a solar start-up called Semprius. The company has already made photovoltaics that are 37% efficient and recently received its first order for a small system.

    Rogers's research has recently veered into biology, with an ambitious goal: integrating electrical and optical devices with living tissue. Other groups have been making a similar push, but Rogers says some of them have used conventional rigid silicon electronics to make what he calls “bricks on straps” and “chips on tapes”: devices such as heart monitors that must be strapped or taped to a subject. “Evolution has come up with lots of solutions to challenging problems,” Rogers says. “None of those look like a silicon wafer.”

    Rogers's solution was to change that look. He and his colleagues have made electronic arrays that can be mounted on extremely thin, flexible plastic sheets, or even on a type of silk that slowly dissolves when implanted in tissues. In the 18 April issue of Nature Materials, they reported using an electronic array to map the electrical activity on the surface of the brains of cat models. They are now working toward using such implantable arrays to prevent future seizures in patients with epilepsy by disrupting the synchrony characteristic of an epileptic seizure.

    In a paper that appeared online 24 March in Science Translational Medicine, Rogers and colleagues from the University of Pennsylvania and Northwestern University in Evanston, Illinois, reported implanting an array of 2016 silicon transistors on thin, flexible plastic film to record electrical activity from the beating heart of a live pig. Someday such devices might be used to treat arrhythmia, both by recording electrical activity in heart cells and by delivering bursts of radiofrequency pulses to kill small patches of cells that are triggering irregular heartbeats.

    Finally, Rogers and his colleagues have developed low-cost, highly efficient micro light-emitting diodes (LEDs). Not only might such devices revolutionize home lighting, but the group is working on ways to implant them in tissues to make what amount to LED tattoos. Hipster appeal aside, Rogers suggests that micro-LEDs might be integrated with biochemical sensors to warn of dangerous medical conditions. Out there? Perhaps. But if Rogers is right, the next semiconductor revolution could reach far beyond your desktop.

  11. News

    Late for the Epidemic: HIV/AIDS in Eastern Europe

    1. Jon Cohen

    The virus spared the region until the mid-1990s; treatment is becoming widely available, but prevention programs raise political antagonism.

    Desperation.

    Sasha has been waiting for months to join an opiate-substitution program in Ukraine.

    CREDIT: MALCOLM LINTON

    When the iron curtain fell in 1991, Eastern Europe and Central Asia were barely touched by HIV. According to the most authoritative estimates of HIV's prevalence, it was the least affected region in the world. Russia, the largest country, had fewer than 1000 reported cases, and hundreds of those were children who had been accidentally infected in hospitals. Many public health officials in the region believed the AIDS epidemic raging elsewhere would make few inroads in their societies. This was a disease spread by gay sex, drug injections, promiscuous heterosexual partnering, and prostitution—behaviors, they thought, their cultures rejected so thoroughly that HIV didn't stand a chance. Today, the Russian Federation and Ukraine alone have twice as many HIV-infected people as all of Western and Central Europe combined. And in an increasing number of countries in the former Soviet Union, ВИЧ, Russian for HIV, is no longer a foreigner's problem.

    At the end of 2008, according to a December 2009 report from the Joint United Nations Programme on HIV/AIDS (UNAIDS), the number of infected people in the region totaled 1.5 million—a jump of 66% from 2001. “Eastern Europe and Central Asia is the only region where HIV prevalence clearly remains on the rise,” the agency concluded.

    The first signs that the epidemic was poised to explode came in 1995. But despite subsequent warnings from UNAIDS and others, few governments in Eastern Europe and Central Asia have made concerted efforts to slow the spread of the virus, and some have defiantly rejected methods that have worked elsewhere. “In all of the regions of the world, it was possible with awareness and prevention to stop the growth, and yet the epidemic is still growing here,” says Dennis Broun, the UNAIDS regional director based in Moscow. Although the driving force is injecting drug users (IDUs) sharing needles, the Russian government in particular has refused to embrace “harm reduction” strategies, such as distributing methadone, a substitution treatment for heroin and other opiates, and exchanging needles and syringes, that have stymied the virus elsewhere. “It's a pity,” Broun says.

    Today, Russia and Ukraine account for more than 90% of the infections in the region. This spring, Science traveled to both countries and met with public health officials, researchers, clinicians, nongovernmental organizations (NGOs), vulnerable groups, and infected people. The countries have responded to the epidemic differently in some key ways—Ukraine, for example, in December 2007 legalized methadone importation (see p. 165)—reflecting their different resources, political climates, and cultures. But ultimately, they face many of the same challenges in both treatment and prevention, as they wrestle with antiquated health care systems from the Soviet era, patchy epidemiology, the increasing spread from IDUs to their sex partners, rampant tuberculosis, staggering infection rates in drug-using street youth (see p. 170), corruption, police brutality (see p. 169), isolation from the West, and weak and fractious research communities (see p. 173).

    Many on the frontlines of combating the epidemic in both countries stress that great strides have been made in preventing mother-to-child transmission and providing anti-HIV drugs for treatment. But they have become deeply frustrated by many other aspects of the response to their epidemics—particularly the limited help available for IDUs, who often are reviled. “It's kind of a hopeless situation,” says Anya Sarang, a sociologist in Moscow who heads the Andrey Rylkov Foundation for Health and Social Justice and studies IDUs and HIV. “But that's our reality.”

    Sarang will be one of the plenary speakers next week at the 18th International AIDS Conference, which the International AIDS Society decided to hold in Vienna—“the gateway” to Eastern Europe—to help change that fatalistic perspective. For the first time, the society will translate all conference material and presentations into Russian, says Robin Gorna, the society's executive director. And she hopes that removing the language barrier, and the meeting's proximity to Russia and Ukraine—as well as to smaller countries in the region with burgeoning epidemics such as Uzbekistan, Kazakhstan, Estonia, Belarus, Moldova, and Latvia—will create a momentum for change that she and others believe is desperately needed.

    Improved responses, however, will require government leadership and accountability coupled with science. To that end, the society has made a great effort to attract government officials from Eastern European and Central Asian countries to the meeting. As of June, a few countries had shown some interest but not, notably, the largest and most influential one, Russia. “Sadly, at the moment we haven't had any of our invitations accepted,” said Gorna. Science's requests for interviews with several Russian government health officials similarly went unanswered.

    Registered complaints

    Theories outnumber facts in attempts to explain why the epidemic in the region took off in the mid-1990s among Ukrainian IDUs (see p. 161). Although mass screening began in the late 1980s, Ukraine had not detected more than 80 cases in a year. But in March and April of 1995, more than 1000 IDUs tested positive in two Ukrainian cities, Odessa and Nikolayev. Some 12,000 diagnoses were reported the next year, and the cases more than doubled by 1997. The majority were IDUs.

    Russia in 1995 had only 1062 total reported cases, and a mere seven were IDUs. But the next year alone, Russia detected more than 1500 infections, and three times that number in 1997—60% IDUs.

    Double trouble.

    Ukraine and the Russian Federation account for more than 90% of the cases in the region.

    SOURCE: UNAIDS

    As the number of HIV cases in both countries steadily grew, the limitations of their epidemiology became increasingly apparent, and today, vast differences separate government figures from those put out by UNAIDS. Russia and Ukraine count only “registered” HIV infections, which means people who come into the health care system and high-risk groups such as prisoners and identified drug users. No effort is made to assess the prevalence in men who have sex with men, a large high-risk group that is heavily ostracized and virtually ignored throughout the region by official HIV/AIDS efforts. UNAIDS and most countries outside the former Soviet Union combine officially reported cases with extrapolations from studies of high-risk groups and household surveys. “We don't have epidemiology here,” complains molecular biologist Andrei Kozlov, who heads the Biomedical Center in St. Petersburg, the region's largest HIV/AIDS research lab.

    UNAIDS's Broun says the Russian case count, or prevalence, clearly understates the true figure because many IDUs fear being registered in databases as drug users and avoid health care facilities because of stigma and discrimination. People also often do not seek care until they have been infected for years and suffered substantial immune destruction.

    At the end of 2007, the latest available UNAIDS estimate, 940,000 people in the Russian Federation—1.1% of the adult population—were infected with HIV. Russia's Federal Research and Methodological Center for AIDS Prevention and Control reported at the end of October 2009, nearly 2 years later, just 516,167 registered cases.

    Alexey Mazus, head of the well-appointed Moscow AIDS Center that provides care and treatment for city residents, staunchly defends his government's official figures, insisting that they capture almost every infected person. “I have no belief in UNAIDS,” Mazus says.

    The official Ukrainian numbers, 161,119 at the end of 2009, similarly differ dramatically from the UNAIDS estimate of 440,000 in 2007. According to UNAIDS, Ukraine has an adult prevalence of 1.6%, the highest in all of Europe.

    The registration system in Ukraine has the same shortcoming as the one in Russia, but it has an additional problem, says Yuri Kobyscha, an epidemiologist in Kyiv who works with the World Health Organization (WHO). In Ukraine, individual states must pay for HIV tests, and many are cash strapped. “States often only test blood donors and pregnant women,” he says. “So people in the most at-risk populations then don't have access.”

    In flux.

    As transmission shifts from injecting drugs to sex, Russia's and Ukraine's epidemics have slowed, but Siberian cases recently spiked. Note official numbers of “registered” cases differ from UNAIDS's estimates.

    SOURCES: CHARLES VITEK, U.S. CDC (LEFT); UKRAINE AIDS CENTER (RIGHT); RUSSIA'S FEDERAL RESEARCH AND METHODOLOGICAL CENTER FOR AIDS PREVENTION AND CONTROL (BOTTOM)

    Outside Russia and Ukraine, no country in the region topped 16,000 infections by 2007, but tiny Estonia and Latvia had higher prevalence rates—1.3% and 0.8%, respectively—than any country in Western Europe.

    Coming up next

    Confusion over the number of infected people pales next to the unknowns about the rate at which new infections are occurring—the incidence—which ultimately determines the epidemic's direction and how prevalence will change. Although a few rigorous studies have followed cohorts of uninfected IDUs to track new infection rates, researchers mostly look at fluctuations in the number of newly registered cases as a crude indicator. Some evidence suggests that the Russian and Ukrainian epidemics have stabilized and will not grow as large as once feared, yet a dearth of hard data mixed with increased spread in new locales make most prognosticators extremely cautious.

    Past predictions about Russia's epidemic in particular have proved wide of the mark. The U.S. National Intelligence Council in 2002 projected that Russia today would have up to 8 million infections—and an adult prevalence rate of 11%. Alexey Bobrik, a director of the Open Health Institute in Moscow, says, “We should be quite realistic that we will not be decimated by HIV. We'll have more people die from car accidents and alcohol each year than from HIV for the foreseeable future. It's a public health problem, but not a public health priority.”

    Bobrik doubts that Russia will transition from a “concentrated” epidemic that is largely IDU driven to “generalized” spread, which is defined by prevalence above 2%. He notes that new registered cases peaked in 2001 at just under 88,000, and although there has been an uptick in official cases since 2006, the growth has been relatively stable, at about 10% per year. Epidemiologist Charles Vitek, who runs the U.S. Centers for Disease Control and Prevention office in Moscow, agrees. “I still don't see much in the way of evidence of a sustained, expanding epidemic in the general population,” he says. “The number of new infections here is modest.”

    Yet Vitek and Bobrik stress that most of the new infections could have been averted with better harm-reduction programs. Vitek further cautions that Siberia recently has seen steep jumps in prevalence rates (see map).

    Epidemiologist Robert Heimer of the Yale School of Public Health is far from convinced that the worst is over. “Since so little prevention is being done and few of the efforts are directed at stopping the source of the epidemic, there's the potential to see the transition from a concentrated epidemic in drug users to one in the generalized population,” says Heimer, who has conducted several incidence studies in Russian IDUs. “That's never been seen on the planet.” Working with the Biomedical Center, Heimer has used different methods to assess incidence in IDUs and found that between 2005 and 2008, annual new infection rates ranged from 14.1% to 20.4%. “That's not a stable epidemic,” he says.

    Ukraine has no incidence data, says WHO's Kobyscha, although the increase in registered cases has slowed. Kobyscha notes that prevalence in IDUs between 20 and 24 years old has plummeted from a high of nearly 30% to just over 8% in 2008, and sexual transmission eclipsed drug injection for the first time, suggesting that the country had reached the “saturation point” at which HIV has already infected the drug users who take the most risks. “We expect that in 2 or 3 years we'll reach a plateau stage,” Kobyscha says.

    Drug-drug interactions

    On a chilly March night in St. Petersburg, social worker and psychiatrist Natasha Shuter asks the driver of her van to pull off a wide highway on the outskirts of the city and stop in front of a pay parking lot. Save for a man inside the guard tower at its entrance, the dimly lit lot looks eerie and lifeless, but Shuter, who works with the locally based NGO Stellit, knows better. She makes a call on her mobile phone, and minutes later, a 28-year-old woman emerges from one of the parked cars, resplendently dressed in a fur coat and knee-high black leather boots.

    The woman, Tatyana, warmly greets Shuter, who for several years has helped the few dozen women who sell sex in this lot, educating them about HIV, providing condoms, and arranging doctor visits. Tatyana takes a seat in the van and catches Shuter up on her life. Tatyana started using heroin at 17 and learned that she was infected with HIV 5 years ago. Although she has been arrested repeatedly and worries for her safety, she can't imagine leaving the business unless she quits the drug. “It's heroin that decides,” Tatyana says. But Shuter can do little to help Tatyana kick her habit, short of referring her to a narcologist, a practitioner of a Soviet-era brand of psychiatry that has little success. So she tries to encourage Tatyana to receive proper care for her HIV infection, but that, too, is a challenge.

    No plateau.

    UNAIDS's Denis Broun says Eastern Europe is the only region in the world with a growing HIV/AIDS epidemic.

    CREDIT: MALCOLM LINTON

    As Tatyana explains, she does not know whether she has suffered enough immune damage to be eligible for treatment because she has not had her blood tested to see how much the virus has depleted her CD4 white blood cells. “It's very difficult to find time to get tested because of my working schedule,” she says. “And until there's a great problem, there's no great reason to do this. Until the cork pops out, you don't do anything.”

    Shuter sends Tatyana off with a big bag of condoms to distribute to friends. “It's very difficult to break the cycle of the lifestyle,” Shuter says. “They work, sleep, wake up, go to the dealer, go to work.”

    Russian AIDS centers have modern monitoring equipment, and access to anti-HIV drugs has steadily improved, with an estimated 66,000 people on treatment in December 2009. Still, IDUs in need often slip through the cracks. The same holds true in Ukraine, which has about 16,000 people on treatment. According to UNAIDS, Eastern Europe and Central Asia had reached just 22% of the people most in need of antiretroviral drugs (ARVs) by December 2008—half the coverage achieved in sub-Saharan Africa. “It's not difficult to get ARVs,” says molecular epidemiologist Elena Dukhovlinova of the Biomedical Center. “It's difficult to get patients to them.”

    A private matter.

    Natasha Shuter and the NGO Stellit—not the Russian government—do outreach with a heroin-dependent, HIV-infected sex worker.

    CREDIT: MALCOLM LINTON

    Psychologist Alla Shaboltas, who works with Dukhovlinova, surveyed people outside the AIDS center in St. Petersburg and found that only 30% were IDUs. “They should be the biggest portion of the population at the stage of AIDS,” says Shaboltas. She says barriers to treatment exist within both the IDU and medical communities. Many IDUs, like Tatyana, don't perceive that they urgently need monitoring and care, or they believe that ARVs are dangerous. Physicians, she says, often worry that IDUs won't adhere to their treatment schedule and tell the patients they can't start ARVs until they stop using drugs. “They lie to them,” Shaboltas says. Many IDUs also wind up in prison, where all health care is patchy.

    On top of these obstacles, Russia and Ukraine have user-unfriendly health care systems: HIV, TB, and drug dependency are each treated in their own centers. There have been improvements since the Iron Curtain fell, says Shaboltas, “but you are in the Soviet system.”

    Both countries have attempted to integrate care, and Ukraine even distributes methadone at a few clinics that also treat HIV and TB. But Ukraine estimates that only 5000 IDUs were receiving opiate substitutes as of January 2010, a fraction of those in need. “It's not a problem,” says Konstantin Lezhentsev, a clinician and harm-reduction advocate in Kyiv. “It's a tragedy.”

    Their own clock

    Despite the many frustrations faced by people combating the spread of HIV in Russia and Ukraine, ARVs have extended many lives. As Lezhentsev visits the Kyiv City HIV/AIDS Prevention and Control Center, he stops outside the morgue. “Nine of my best friends and 15 of my patients ended up there,” he says. For the first time since it started tracking HIV, Ukraine recorded a drop in AIDS deaths last year. Russia similarly has seen a drop in AIDS deaths since 2007.

    Olena Kravchenko, who heads outpatient treatment at the Kyiv AIDS center, points to what she calls her old “computer” that she had when they opened their doors 10 years ago: a three-ring binder. Kravchenko had little she could offer patients then other than an HIV test, and she had scant information about the disease in a language she understood. Today, thanks to money from the Global Fund to Fight AIDS, Tuberculosis and Malaria, her clinic treats 1300 adults and 120 children and monitors their CD4 counts and HIV levels in their blood. There are computers everywhere. The clinic also does TB diagnosis and has an IDU community center where they can exchange needles.

    Yes, Kravchenko has a long wish list, and she disparages her government for relying on outside funding to address the country's HIV/AIDS problem. But she is resigned to the fact that progress has to be measured by its own clock here, and they often lag far behind their Western European neighbors. “The more we're developing, the more we want to work on international standards,” she shrugs. “There's nothing perfect in this world.”

  12. News

    Tracing the Regional Rise of HIV

    1. Jon Cohen

    Detailed molecular analyses have revealed that HIV strains isolated in Belarus, Russia, Kazakhstan, and other countries in the former Soviet Union evolved from southern Ukrainian strains. But the factors behind the explosion of HIV in this region remain elusive.

    Explosive concoction?

    Some blame the manufacture and distribution of chernaya for sparking the epidemic.

    CREDIT: MALCOLM LINTON

    ODESSA, UKRAINE—Abundant epidemiologic evidence shows that the HIV epidemic that has startled Eastern Europe traces back to this charming Black Sea city in the early 1990s, right on the heels of the fall of the Soviet Union and the resultant economic, cultural, and political upheaval. Without question, injecting drug users (IDUs) drove it. And detailed molecular analyses later revealed that HIV strains isolated in Belarus, Russia, Kazakhstan, and other countries in the former Soviet Union evolved from the southern Ukrainian strains (see graphic). But the factors behind the explosion of HIV in this region remain elusive.

    Part of the confusion revolves around the drugs that people inject, their networks, and the way drugs are prepared and shared. HIV typically piggybacks on heroin, which has played a major role in the Russian epidemic. But here in southern Ukraine, heroin was not popular 15 years ago.

    In Ukraine, Russia, and other Eastern European countries, people have long injected liquid poppy straw, or chernaya, a homemade opiate cooked from the cheap remains of plants harvested for their seeds, which are used in food or pressed for oil. According to several IDUs interviewed here, people started to sell syringes pre-filled with chernaya in the early '90s, which were convenient but introduced new opportunities for HIV to spread. One commonly voiced thesis is that the Roma, a “gypsy” community in Odessa that prepares and sells the prefilled syringes, picked up used syringes off the street.

    Social psychologist Robert Booth of the University of Colorado, Denver, has interviewed IDUs and dealers in Ukraine since 1998, and he doesn't believe that Romas kick-started the epidemic. “I'm sure there are some cases where people got used syringes, but it's more dangerous if they go to a dealer,” says Booth.

    Many dealers are users themselves. Booth contends that the way they prepare chernaya and a widely used ephedrine-based drug called vindt may indeed have spread HIV. In a 2003 study, Booth and his colleagues reported that dealers typically cook poppy straw with chemicals to make a solution of drug, draw it into their own syringes, and then squirt it into a buyer's syringe, or directly fill the user's syringe from the batch. “You have numerous syringes going into a common container and pulling out the solution,” says Booth. “If anyone has HIV or hepatitis C, you're passing the virus through the solution.”

    Hitchhiker's guide.

    HIV subtype A followed heroin trading routes (arrows) into Eastern Europe; subtype B predominates in the west.

    CREDIT: SOURCES: UN; BIOMEDICAL CENTER

    Interview-based research does not provide hard evidence of routes of transmission, however. Epidemiologist Robert Heimer of Yale University School of Public Health has gone to considerable lengths to assess whether these chernaya practices spread HIV. Working with Andrei Kozlov's team at the Biomedical Center in St. Petersburg, Russia, and Jean-Paul Grund at the Center for Addiction Research in Utrecht, the Netherlands, Heimer manufactured chernaya in his lab (with permission from the U.S. Drug Enforcement Administration). The researchers then spiked the chernaya with HIV-infected blood to simulate the contamination of the solution by a dirty syringe or by directly adding blood (a method used to remove impurities). In another test, they drew HIV-infected blood into syringes, discarded most of it, and then filled the syringes with chernaya or a saline control.

    As the researchers reported in the May 2006 issue of Addiction, if HIV-infected blood contaminated the chernaya solution, heat and chemicals killed the virus. In the HIV-contaminated syringes, those rinsed with saline had viable HIV, whereas only 43% of those with chernaya did. So the drug reduced the risk of HIV being transmitted through a dirty needle. “It's completely impossible for contaminated chernaya to have been the root of the epidemic,” says Heimer.

    Sharing of syringes filled with chernaya may initially have spread HIV in southern Ukraine, but Heimer and co-author Grund say the epidemic fully blossomed in Russia with the increased supply of plentiful and potent heroin from Afghanistan. “It's the freemarket system acting in the most open way in a completely unregulated market,” says Heimer. Heroin and opium seizures in Russia charted by the United Nations Office on Drugs and Crime indeed show a steep increase that begins in 1994.

    Heimer says the novelty of heroin in Russia contributed to HIV's spread there in the '90s, and its popularity is now on the wane, with his research showing a steadily increasing age of the average user. But he warns that IDUs are still being infected with HIV at a high rate and adds that this is no time to be complacent. “All of these epidemics of drugs follow the same cyclical patterns,” says Heimer. “The question is, What will happen if the pattern recreates itself?”

  13. News

    No Opiate Substitutes For the Masses of IDUs

    1. Jon Cohen

    Methadone can slow HIV's spread, yet Russia outlaws the drug, and Ukraine, which only recently made it legal, struggles to meet demand.

    Giving thanks.

    Methadone has freed Sergey Nenov from opiates and put him on a road to health.

    CREDIT: MALCOLM LINTON

    KYIV, ODESSA, AND DNIPROPETROVSK, UKRAINE; MOSCOW AND ST. PETERSBURG, RUSSIA—On Easter Sunday, Sergey Nenov, along with hordes of other people in Odessa, took a basket filled with sprinkle-covered frosted cake, cookies, and other offerings to a gold-domed Orthodox church and lit candles in prayer. But when Nenov came to a gilded painting of the Madonna and Child, he separated himself from the crowd by pressing his lips to glass that protected the Christian icon. Nenov had reason to be grateful this year. He is one of 4300 opiate addicts in the country to receive methadone, a substitution treatment that has freed him from his dependency, allowing him to stop having run-ins with the law and, at long last, begin to tackle his dual infections with HIV and tuberculosis (TB).

    Nenov, who lives at a TB hospital in the city that dispenses his daily dose of methadol—a pill form of methadone—started injecting chernaya, an opiate made from liquid poppy straw (see p. 161), in 1988. He is astonished that he survived long enough to see the substitute opiate come to Ukraine; importing it was illegal until December 2007. “Before, we would watch TV reports about these Dutch substitution treatment programs and say, ‘It will never happen in our country,’” says Nenov.

    Opiate substitutes are one component of harm reduction, an international movement that promotes treatment rather than arrest and incarceration of injecting drug users (IDUs). The harm-reduction “package,” which aims to protect IDUs from infections and other health risks, also includes clean needles, counseling, HIV testing, and education. In a 2005 position paper, the Joint United Nations Programme on HIV/AIDS (UNAIDS), the World Health Organization, and the United Nations Office on Drugs and Crime explicitly backed opiate substitutes to prevent HIV's spread. An expert committee convened by the U.S. Institute of Medicine in 2007 cited “strong evidence” that methadone and another popular substitute, buprenorphine—now used by only 800 others in Ukraine—reduced illicit drug use and HIV-risk behaviors such as sharing injecting equipment. It recommended that they “be made widely available, where feasible.”

    Although Ukraine, Russia, and other countries in the former Soviet Union have IDU-driven HIV/AIDS epidemics that are increasingly spreading into the broader population through sex, harm reduction remains spotty throughout the region. Even the Ukrainian government has not fully embraced harm reduction, which is largely delivered by nongovernmental organizations (NGOs) that receive support from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Ukraine's 2010 HIV/AIDS progress report to the United Nations, endorsed by the minister of health, acknowledges the short comings: “The scope, scale, quality and intensity of HIV prevention activities among the most vulnerable population groups remain insufficient to stop HIV spreading in these groups and limit the potential spread of HIV among the general population.”

    Russian roulette

    In comparison, the Russian Federation seems outright hostile toward harm reduction, to the outrage of researchers, public-health specialists, and activists. The banning of opiate-substitution treatment (OST) has evoked the sharpest criticism. “OST does not exist in Russia, and it's the place where it's most needed,” says UNAIDS's Denis Broun, the Moscow-based regional director for Europe and Central Asia. The government does offer treatment at “narcologic” clinics, but one recent study found a 90% relapse within a year among nearly 1000 users who sought help.

    Unlike in Ukraine, the Russian government pays no heed to civil society's input, charges Anya Sarang, who specializes in drug policy and runs the Andrey Rylkov Foundation for Health and Social Justice in Moscow. “The government on every level—federal, city, oblast—they're never interested in listening to the community,” Sarang says. “All the decisions here are totally political and unsupported by evidence. They don't make any effort to find out what's going on in the world.”

    Prickly issue.

    A Kyiv NGO provides free needles and collects used ones, but Moscow says nyet.

    CREDIT: MALCOLM LINTON

    Adding to the lack of knowledge about the benefits of harm reduction, there's a “huge stigma” toward drug users, notes psychologist Alla Shaboltas, who studies IDUs at the Biomedical Center in St. Petersburg. “They've never been considered normal people who deserve treatment,” says Shaboltas. “They're considered criminals who should die.”

    Several Russian public-health officials and politicians did not reply to Science's request for interviews over several months, but Alexey Mazus, head of the city-sponsored Moscow Centre for HIV/AIDS Prevention and Treatment, articulates the government position—which he shares—and makes it clear that he strongly objects to other countries criticizing his country's stance toward harm reduction. “It's not their business what's going on in the Russian Federation,” says Mazus.

    In his view, the evidence that OST and other harm-reduction interventions worked in some countries has no bearing on Russia. “Take into consideration whether people are the same in terms of culture and psychology,” Mazus says, stressing that injection drugs like heroin are new to his conservative country. Giving a heroin user methadone, he says, is “like a doctor who tries to treat an alcoholic and gives the patient alcohol.”

    Similarly, he thinks that needle exchange—which is not allowed in Moscow—would “energize drug using. What is more, it will show that our government tolerates using drugs—and they're firmly against it, just like the whole society.”

    Russia has allowed a consortium of NGOs known as GLOBUS to run harm-reduction projects, which include needle exchange in many locales, with money from the Global Fund, but the government recently reneged on a promise to bankroll those efforts itself (see p. 168). “The Russian government says it's doing this because of lack of effectiveness,” says Charles Vitek, head of the Global AIDS Program in Moscow for the U.S. Centers for Disease Control and Prevention (CDC). “It's hard to say what type of evidence would be sufficient to change the government's stance.”

    Alexey Bobrik of the Open Health Institute in Moscow, who heads GLOBUS, says harm reduction, and in particular OST, is essentially an ideological issue. “In Russian culture, science almost doesn't matter,” says Bobrik. “It's similar to the Soviet Union and questioning the superiority of socialism. Regardless of whether you could support your argument with data, you'd be labeled as insane, an unnecessary person. The same with OST now.” But if someone in a high enough position decides to back OST, the opinions of drug-control specialists and HIV experts won't matter. “If Putin says we should try OST,” says Bobrik, “it will be done.”

    CREDIT: MALCOLM LINTON

    Ukraine's gains and pains

    In the industrial city of Dnipropetrovsk, the City Clinical Hospital No. 21, built in 1908, looks its age. The sprawling institution sits on a steep hill and houses clinics in several low-slung buildings with corrugated tin roofs and heavy steel doors that are shielded by ornate awnings, some buckled with rust. Windows are boarded in places, and gates tilt on their hinges. It seems an unlikely place for one of the country's most modern and ambitious programs for HIV-infected IDUs, offering them OST, TB treatment, and antiretroviral drugs (ARVs) all at the same facility.

    Each morning, the 48 IDUs in the program, which started in July 2008, gather at the OST clinic for their daily dose of methadol. They hang out on the front steps and smoke cigarettes while they wait their turn, and though some grumble about the drug killing their sex drive and the hassle of making daily visits to the clinic, there's wide agreement that the methadol is helping them lead what several refer to as “normal” lives. “The program is great,” says Vlad, 45, on a drizzly and drab April morning. “I don't have to steal or hide from the police. Everything is cool.”

    Vlad and his wife, Natasha, 49, walk into the clinic and enter a small, tidy room at the front. After they sign in and a nurse checks their names off her own list, Alonya Lesnichaya, the doctor who runs the program, places their individual doses of methadol pills into plastic cups and pestles them into tiny chunks. One after the other, they toss the medicine into their mouths, chase it down with a sip of soda, and then open wide to show Lesnichaya that they have swallowed everything. The elaborate ritual has less to do with making sure that they received the methadol than the concern that they might hide it in their gums and later spit it out and sell it on the black market.

    The potential “diversion” of substitute opiates is one of several reasons that Lesnichaya says many doctors on the staff did not initially support the idea of opening the OST clinic here, which is supported by the Clinton Health Access Initiative and a Global Fund grant monitored by the International HIV/AIDS Alliance in Ukraine. “Mainly, they were afraid it would turn out to be a drug-dealing place,” says Liudmila Timoffeva, the director of the hospital. Lesnichaya adds that they also had to confront unease from other patients. “We didn't want to frighten people, and we worried that our society was not ready.” But “we made it work,” she adds, establishing “a very close, integrated link between the different specialists.”

    Hard to swallow.

    Alonya Lesnichaya (lower right) says hospital staff at first resisted an integrated HIV/TB/methadone program for IDUs, but it's working well.

    CREDITS: MALCOLM LINTON

    The clinic currently helps just a tiny number of people in Dnipropetrovsk, one of the cities hardest hit by HIV in the country, and there is only one other OST program operating here. And progressive as this program may be, it accepts only HIV-infected IDUs. Lesnischaya says they were put first in line because when they're using or preoccupied with trying to score and avoid withdrawal, they have great difficultly remembering to take their ARVs on time or even where they put them. But that shuts out IDUs like Sasha, who badly wants into the program.

    A 35-year-old carpenter who lives with his mother in a nine-story tenement on the outskirts of the city, Sasha began using when he was 17. Now estranged from his wife and 1-year-old child, he works with an NGO, Way to Life, that also provides counselors to the program at City Clinical Hospital No. 21. Representatives from Way to Life come to visit him to drop off bags filled with clean needles, which he will then distribute to other users. He becomes sullen and angry when the Way to Life outreach workers explain that the OST program cannot take him because he is not infected with HIV.

    Sasha carries the bags of needles into his bedroom and places them on a vanity next to a copy of the Bible. On the mirror, he has taped up a little prayer that reads, in part, “My God, I don't want to be dependent.” He takes a long look at the floor. “I pray, and it doesn't help,” he says.

    Future prescriptions

    The IDUs in Ukraine and their advocates have begun pushing to expand OST—which the Global Fund estimates now reaches only about 10% of the IDUs in need—and improve it. “Substitution treatment has a huge number of problems,” says Iryna Borushek, a leader of the All-Ukrainian Network of People Living with HIV who sits on the country's coordinating mechanism that prepares and oversees Global Fund grants for the country. Borushek, a buprenorphine recipient herself, says at the top of the agenda is doing away with the requirement to make daily trips to an OST clinic. “People are chained to the site,” she says. In all of Ukraine, only six people have prescriptions for OST that allow them to take the drugs without being observed.

    Psychologist Olga Belyaeva, who runs an NGO in Dnipropetrovsk that helps IDUs, is one of the six Ukrainians who has a buprenorphine prescription. She and other community activists are lobbying for national regulations that will establish standards of care for substitution treatment, federal funding for it, and more flexible use of different substitution drugs. “We need political will from the new government to change the drug policy more to public health,” says Belyaeva.

    Some fear, however, that Ukraine's new president, Viktor Yanukovych—who was elected in February and has closer ties to Moscow than his predecessor did—will not be receptive to expanding OST. “The legalization of methadone in Ukraine was a hardfought battle, and like many things, it may be vulnerable because of political changes there,” says CDC's Vitek, who is relocating to Kyiv in August. “If groups could seize on any evidence of a lack of effectiveness, methadone overdose deaths, or diversion, there's a continued political risk.”

    For Belyaeva and other activists, any rollback of Ukraine's hard-won policies toward those of Russia would be disastrous. “When I was in Moscow in November,” says Belyaeva, “I came back home and was kissing the ground.”

  14. News

    Praised Russian Prevention Program Faces Loss of Funds

    1. Jon Cohen

    In 2006, then-President Vladimir Putin pledged increased support for HIV/AIDS programs, but the government recently declined to fund some key efforts.

    On 21 April 2006, Vladimir Putin, then president of the Russian Federation, unexpectedly called for increased spending and urgent new measures to combat HIV/AIDS. “We need more than words; we need action, and the whole of Russian society must get involved,” Putin declared.

    Putin's critics long had accused him of turning a blind eye to the country's epidemic; a 2004 report from Human Rights Watch complained that “the Russian government has for too long been acting as though HIV/AIDS is little worse than hemorrhoids.” In particular, Putin and his underlings did not support harm-reduction efforts that aimed to slow the spread of HIV among injecting drug users (IDUs), who account for most infections in the country. Nor did the government target prevention efforts to other vulnerable groups like sex workers and men who have sex with men. Nongovernmental organizations (NGOs) picked up the slack and launched their own projects, receiving substantial financing from the Global Fund to Fight AIDS, Tuberculosis and Malaria.

    Skeptics linked Putin's sudden concern for HIV/AIDS to Russia's first hosting of the annual Group of Eight (G8) summit, which would take place in St. Petersburg in July 2006. “He wanted to show we are normal people and care about HIV,” says Alexey Bobrik, a clinician and director at the Open Health Institute, an NGO in Moscow. “It was much less sensitive than nuclear proliferation or other problems.”

    The Russian government did for a time take dramatic action. At the G8 summit, Russia announced that it would shift from being a Global Fund recipient to a donor. In another generous move, it pledged to reimburse the fund for the $217 million that Russian grantees—mainly NGOs—were slated to receive between 2007 and 2010 and also offered $40 million to help Africa. The 2007 federal Russian HIV/AIDS budget grew to $445 million—a 57-fold increase from 2005. And the government indicated that it would finance efforts aimed at high-risk groups.

    The Russian NGOs working on HIV/AIDS were elated, if wary. They had organized themselves into a consortium, Global Efforts Against HIV/AIDS in Russia (GLOBUS), led by Bobrik and operating in 10 different regions. Nearing the end of a 5-year Global Fund grant of nearly $90 million, GLOBUS in May 2008 took heart when Russia's minister of health and social welfare, Tatyana Golikova, assured delegates at the 2nd annual Eastern Europe and Central Asia AIDS Conference (EECAAC), held in Moscow, that GLOBUS's work was appreciated. According to a press release from her office, “all projects and programs that were initiated by nonprofit organizations must be continued.”

    Climate change.

    Vladimir Putin's (above) bold HIV/AIDS stance has weakened, leaving the Global Fund to rescue Alexey Bobrik's (below) NGO consortium.

    CREDITS (TOP TO BOTTOM): G8 RUSSIA (WWW.EN.G8.RUSSIA.RU); MALCOLM LINTON

    Yet in July 2009, a month before the end of the GLOBUS grant, Bobrik received word that the government would not bankroll the consortium after all. Several other NGOs had to lay off employees or close up shop. One is LaSky, a prevention project for men who have sex with men in St. Petersburg. “Our clients have no place to go,” says Ilya Kurmaev, who runs the effort. A recent study by Stellit—another NGO in the city—found a prevalence in that population approaching 12%.

    Evgeniy Petunin, who is based in Moscow and heads the Russian Harm Reduction Network—an NGO that has depended on Global Fund money—says the government has no specialists who work with IDUs. “Harm reduction in Russia is dying,” says Petunin. “The government doesn't pay attention to the problem.”

    Nicolas Cantau, the portfolio manager for the Global Fund in charge of the GLOBUS grant, says a battle between government agencies led to the sudden change of heart about supporting GLOBUS: The health ministry argued that it made more sense to promote “healthy lifestyles” to prevent HIV infection than to back ineffective harm-reduction programs. “There's been an ideologically based approach as opposed to following scientific evidence,” says Cantau. “GLOBUS is one of the most successful programs worldwide since the beginning of the Global Fund.”

    Complaints about the government's decision to abandon GLOBUS took center stage in October 2009 at the 3rd EECAAC, again held in Moscow. Attendees included Michel Kazatchkine, the head of the Global Fund, but no one came from the Russian health ministry. The next month, the Global Fund's board, on “an extraordinary basis” that recognized “an emergency situation,” awarded GLOBUS $24 million to keep the consortium alive through 2011. “There's a lot of concern about the future,” says Cantau. “It's just for 2 years, and 2 years is going to pass very quickly.”

    Bobrik has mixed feelings about the emergency grant; he's grateful to the Global Fund but says the new money lets the government off the hook for two more years. Maia Rusakova, a sociologist who runs Stellit, similarly contends that Russia must support these efforts at the local and federal level. “Our politicians know how to look quite nice and they say a lot of things, but they don't do it,” says Rusakova. “The situation is very, very serious, and I'm concerned that it looks like a ticking bomb.”

  15. News

    Law Enforcement and Drug Treatment: A Culture Clash

    1. Jon Cohen

    A raid on an opiate-substitution treatment center in Ukraine has highlighted the tense relationship between police, injecting drug users, and harm-reduction advocates.

    Open-and-shut case.

    Oleg Vaschenko is one of many clients of this clinic who say a police raid was harassment.

    CREDIT: MALCOLM LINTON

    ODESSA, UKRAINE—On 11 March, Tatyana Afanasiadi went to the Odessa Oblast Narcological Dispensary for her dose of buprenorphine, an opiate-substitution drug distributed there each day along with methadone. Afanasiadi, 31, is not just one of the clinic's more than 200 drug-dependent clients, about half of whom are infected with HIV: She is a lawyer and head of the Union Together for Life, a nongovernmental organization that catalyzed the opening of this pioneering opiate-substitution treatment (OST) program, and she helps run the office. This role thrust her into the middle of a high-profile showdown with police that loudly broadcast the sharp tension throughout Eastern Europe between law enforcement and harm-reduction efforts like OST that are designed to slow HIV's spread.

    According to Afanasiadi, as she was leaving the clinic that Thursday morning, three men dressed in civilian clothes approached, greeted her by name, slapped handcuffs on her wrists, and took her to an unmarked car with tinted windows. “At first I thought it was a scheme where police grab drug users and then ask them to identify another user they're already looking for,” she says. Afanasiadi then worried that they were going to plant drugs on her and demand a bribe, so she stressed that she didn't have any money. When that had no impact, she tried another tack. “I told them I'm ill and tried to frighten them with my HIV infection, but they were knowledgeable, and it didn't work.”

    The men, who she says refused to show identification, took Afanasiadi to their police station. Unbeknownst to her, the clinic was being raided because of allegations that it did not have the authority to distribute substitute opiates and suspicions that staff members, including Afanasiadi, were selling the drugs on the side. At the station, with two female observers present, Afanasiadi had to remove her clothes, which were carefully inspected for stashed drugs. “They were extremely disappointed,” she says. They next sent her to a gynecologist for a vaginal exam. “It was quite a disgusting procedure,” she says of the ordeal. When that turned up nothing, they searched her home, which she shares with her husband and 6-year-old son, and her car. That evening, with no evidence against her, they locked her up. The clinic's doctor, Ilya Podolyan, was also detained, as was a nurse.

    Broken trust.

    Tatyana Afanasiadi says police undermined efforts to convince IDUs who seek help that they'll be protected.

    CREDIT: MALCOLM LINTON

    After a high-powered attorney intervened, the police freed Afanasiadi the next day without charging her. But Podolyan remained in jail for 4 days. The police also confiscated files from the clinic. Without the staff and the records, the clinic remained shuttered, leading to a massive protest by clients that Saturday that attracted much media attention and sent waves of concern that have rippled far and wide. “This is a very dangerous signal,” says Yuri Kobyscha, an HIV/AIDS epidemiologist who works with the World Health Organization in Kyiv. This site, like most OST projects in Ukraine, is supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria.

    The fund's Ukraine portfolio manager, Andreas Tamberg, has strongly condemned the raid and arrests as “a violation of human rights” and “epidemiologically foolhardy.”

    Afanasiadi says the raid on the clinic undermines a broader agenda to encourage injecting drug users (IDUs) to seek help and, if they're still injecting, take advantage of other harm-reduction programs such as needle exchange or treatment and counseling for their HIV infection. “IDUs are really hard to connect with any services,” says Afanasiadi. “We invite people into substitution treatment and guarantee anonymity and protection in some ways, and at the end of the day, we can't guarantee them anything.”

    Since the raid, events have taken a turn for the worse. On 28 May, the Ministry of Internal Affairs in Odessa indicted and rearrested Podolyan, charging him with 42 counts of illegally distributing buprenorphine. The International HIV/AIDS Alliance in Ukraine, which administers the Global Fund grant to the clinic, held a protest press conference on 3 June, documenting that this case is one of several in which police have interfered with OST programs and appealing to the country's general prosecutor to intervene in what it branded the “systematic unlawful criminal prosecution of narcology doctors.”

  16. News

    HIV Moves In on Homeless Youth

    1. Jon Cohen

    Studies have discovered shockingly high HIV prevalence rates in kids who live on the streets of Russia and Ukraine; nongovernmental organizations are trying to give them new leases on life.

    Mean streets.

    Stas Fedorov (center) and his friends have risky lifestyles that HIV easily exploits.

    CREDIT: MALCOLM LINTON

    ST. PETERSBURG, RUSSIA, AND ODESSA, UKRAINE—Russians frequently boast that St. Petersburg is the most beautiful city in the country, and Ukrainians say the same about Odessa. Both feature well-preserved architecture in Italian and French styles that date back to the 18th century, stunning monuments, and lots of water, be it the canals that wind through St. Petersburg pouring into the Neva River or the majestic Black Sea that laps Odessa's shores. Yet both cities have a dark underbelly that has caught the attention of HIV/AIDS researchers: Large numbers of youths living on the street who, as a group, are at as high a risk of becoming infected by the virus as any vulnerable population ever studied. “They're hard to reach and invisible for HIV statistics and often for HIV prevention programs,” says Dmitry Kissin, an obstetrician/gynecologist who works for the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta. “No one knows how many street youth there are because no one's counting them. And when you don't know about something, you don't pay attention.”

    Kissin, who is originally from St. Petersburg, has worked for the past 4 years with colleagues in both countries to bring attention to this underappreciated high-risk group. Estimates suggest that up to 3 million youths are living on the streets in Russia and 150,000 in Ukraine. They live in city shadows, sleeping in basements of apartment buildings and abandoned buildings, taking odd jobs and panhandling, and constantly dodging police. “You don't see them unless you look for them,” he says.

    Kissin has been trying to do just that. Along with CDC's Susan Hillis and co-workers from HealthRight International—a nongovernmental organization (NGO) formerly known as Doctors of the World-USA and founded by pioneering AIDS researcher Jonathan Mann—he launched a study in St. Petersburg in 2006. The researchers identified 41 different train stations, metro stops, street markets, and other sites where groups of teens gathered. They picked half of the sites at random and started enrolling youths in the study. In the end, they signed up 313 teenagers between the ages of 15 and 19, two-thirds of them male, who lived at least part-time on the street, were not cared for by their families, and did not regularly attend school. They questioned the participants in detail about their lifestyles and tested each one for HIV. When they first saw the results, says Konstantin Zakharov, the project coordinator for HealthRight, “it was a shock.” A staggering 37.4% were infected.

    Highs and lows

    Shortly before dark one March night, three young men hanging out together on a canal near the center of St. Petersburg approach a mobile van operated by HealthRight and greet Zakharov. In the wake of their first study, which was published in the 12 November 2007 issue of AIDS, HealthRight started to send the van out on the streets twice each week to do HIV testing and counseling of street youth. The group also opened an overnight shelter, organized a drop-in center for counseling with psychologists, and helped connect youths in need of medical care with the appropriate doctors. The oldest of the three young men, Stas Fedorov, 23, has received vocational training and leads informal, HIV-prevention workshops with others in his situation. His two friends are drinking vodka from a soda bottle, but he seems sober, the wise elder of the group. “My dream is to live like a normal person,” he says. “Start working and restore my documentation, which somebody stole.”

    Fedorov is infected with HIV—“My girlfriend gave me that present,” he says—but he is relatively healthy, which is remarkable given his history. He says he started smoking cigarettes at 6. His friends took him to the big city, St. Petersburg, at 7, and he was dazzled by the bright lights and stayed, sleeping in basements or in abandoned buildings. Like many of the youths, Fedorov was an orphan and got into inhalants and injecting drugs, but he says he is clean now. “I've seen people do anything for the dose,” he says.

    Kissin, Zakharov, and their colleagues have attempted to tease out the risk factors that lead to such high infection rates among street youth—information that is key to tailoring prevention programs to each vulnerable population. Some behaviors are well known to fuel HIV's spread: an astounding 78% of the youths who injected drugs tested positive, as did 70% who had another sexually transmitted infection (an indicator that they did not use condoms). But they also linked HIV infection to social forces particular to street youth. The death of both parents more than tripled the risk of becoming infected, and having no place to live raised it 2.4-fold.

    Shelter from the storm.

    Inna Nikiforova (above) and The Way Home offer street youths a nourishing environment, including a chance to rebuild self-esteem playing sports and winning medals.

    CREDITS: MALCOLM LINTON

    Although many studies have found that people who learn they are infected take precautions not to infect others, in this group, teens who came into the study knowing they were HIV positive were more likely to share needles and inconsistently use condoms. “Maybe there's just a sense of hopelessness among them,” says Kissin. “HIV may not be your first priority when you need to negotiate survival on the street and find food, drugs, alcohol, and some place to sleep.”

    Odessan odyssey

    “Dima! Dima! Dima!”

    Inna Nikiforova is crouching down and yelling through an iron grate that covers an opening to the dirt-floored basement of a downscale apartment building not far from Odessa's swank downtown. Nikiforova, a former injecting drug user (IDU) herself who lost an arm after a suicide attempt as a teen, is an outreach worker with The Way Home, an NGO that helps street youth, and Dima is one of the teens she has become closest to over the years. This Saturday afternoon, she has brought him a plastic crate filled with food, but he is not in his usual haunt, which is strewn with filthy mattresses, trash, cigarette butts, and burnt-out candles.

    Nikiforova soon finds Dima at a nearby busy intersection approaching cars, hat in hand. He has clubbed feet, the result of nerve damage from injecting an ephedrine-based drug called baltushka, and he hobbles over and gives her a long hug, closing his eyes. He has few teeth left. He is 18 but looks much younger. Dima also is HIV infected, as are 27% of the street youth here, according to a study conducted in 2008 by HealthRight and the U.S. CDC. And like many teens who live on the street, he is difficult to help—and is in dire need of assistance. “We found his father in Moldova and said, ‘Here's your kid, he wants to come home,’” says Nikiforova. “The father had a new wife and family and said, ‘He's not my son until he stops using drugs.’”

    The Way Home runs a shelter that houses two dozen street youth, and Nikiforova, who lives with them in the well-kept dorms, brought Dima in. He lasted only 3 days. But clean for a time, joining a soccer team and winning a medal that Nikiforova hangs from a mirror in her bedroom. To return to his father, all he needed was proper documentation—like many street youths, he had none—and The Way Home tried to help him obtain them. Then Dima relapsed. “He just got drunk and left, and since then …” says Nikiforova.

    Attempts to help the street youth are even more complicated when it comes to HIV prevention and care. As Sergey Kostin, the head of The Way Home, explains, they are not allowed to distribute clean needles to the youths. “It's against the norms,” says Kostin, a geologist and former IDU himself. “It's hypocritical.” Nataliya Kitsenko, a clinician who directs the HIV/AIDS program for the charity, says they have had many difficulties accessing anti-HIV drugs for the youths, too. “It's very hard because they don't have parents to give consent,” says Kitsenko. “It's a big problem, and we don't know how to solve it.”

    Although NGOs such as The Way Home and HealthRight have joined with international groups to address the often-ignored epidemic of HIV/AIDS in street youth, Kitsenko doesn't expect her own economically challenged government to step up its efforts anytime soon. “The government doesn't do much of anything for the so-called normal people, and at such times, how can they think of programs for the marginalized?” she asks.

  17. News

    Reducing HIV Infection and Abandonment of Babies

    1. Jon Cohen

    Injecting drug users often seek medical help late in pregnancy and then relinquish their babies to the state. Surprisingly, their drug use is not the major factor.

    Helping hand.

    Evgeny Voronin's work with HIV-infected children and pregnant women has drawn international attention.

    CREDIT: MALCOLM LINTON

    ST. PETERSBURG, RUSSIA—In the late 1980s, when Russia had detected only a smattering of HIV cases, 270 children became infected in several hospitals through the reuse of contaminated needles. “The country was in shock,” says Evgeny Voronin, who then ran an infectious-disease hospital in Ust-Izhora, on the outskirts of St. Petersburg. The Ministry of Health asked for his help, and he opened a pediatric AIDS center to care for the children. “It was very difficult for us,” Voronin says. “The mothers called us murderers. It didn't matter that the children were infected very far from us. They thought all people in white coats were responsible for what had happened.”

    That early effort evolved into the Centre for Prevention and Treatment of HIV Infection in Pregnant Women and Children, which Voronin still runs. Now, rather than caring for accidentally infected children and their grieving mothers, the center focuses on helping infected mothers prevent transmission to their babies and raising HIV-infected children who have been orphaned or abandoned.

    In March, the center's orphanage had only 33 HIV-infected children. “It's not the biggest group we help, but it's the most vulnerable,” says Voronin. His work with HIV-infected children has made him something of a celebrity—visitors have included former U.S. first lady Laura Bush and Western movie stars—and also drawn attention to prevention of mother-to-child transmission (PMTCT) efforts and the country's staggering, post-Soviet explosion of orphaned and abandoned children. In 2002, the Russian government put the number of such children at 700,000.

    More than 50,000 children have been born to HIV-infected women in Russia (half during the past 3 years). Although women increasingly are becoming infected through sex, many are injecting drug users (IDUs), and several studies have attempted to untangle how drug use influences both abandonment and the limited success of PMTCT.

    Susan Hillis, a reproductive health specialist at the U.S. Centers for Disease Control and Prevention—who incidentally has adopted eight Russian children—collaborated with Voronin and other Russian colleagues in analyzing the factors that lead HIV-infected mothers in St. Petersburg to abandon their babies. The study followed 43 HIV-infected women, two-thirds IDUs, who learned their status during labor and delivery. Half of them abandoned their babies, a process that involves relinquishing the child to the state. “Everyone, including all of our Russian colleagues—people we respect and trust—really believed abandonment to be related to injecting drugs,” says Hillis.

    But the data said otherwise: The only significant risk factor was an unintended pregnancy. (Women typically abandon babies before they know the baby's HIV status, so that's not a factor.) “Women who aren't motivated to take care of babies and themselves before delivery are less likely to take care of them afterward,” she says. Hillis, who published these results in the February 2007 International Journal of STD & AIDS, is now working with ob-gyn Anna Samarina at Botkin Hospital here to advocate that more of these women have easy access to contraceptives.

    Hillis and co-workers next examined PMTCT in 1500 HIV-infected mothers in St. Petersburg who gave birth between 2004 and 2007. More than half had a history of injecting drugs—with one-third using while they were pregnant. (Only 11.4% abandoned their babies, which Hillis believes reflects the situation today better than the earlier study did.) They all received anti-HIV treatment to prevent transmission, but many began late in pregnancy, when it is less effective, or used substandard regimens. The study, published online on 3 February in the Journal of Acquired Immune Deficiency Syndromes, found that 6.3% of mothers passed HIV to their babies—about three times the rate seen in Western Europe. Women who injected drugs during pregnancy started treatment later, on average. But factors such as access to prenatal care, rather than drug use per se, were more critical in determining the risk of transmitting the virus. “The most important thing is not whether you're using drugs,” says Hillis. “If we could figure out a way to get them early and give them proper prophylaxis, we could do a tremendous amount to reduce transmission.”

    These efforts with orphans and PMTCT have come full circle for Voronin: Twelve of the girls he cared for when they were infected by hospital procedures came to his center when they were pregnant. None infected their babies. “People ask me why do you do so much for orphans?” he says. “We took in these girls with AIDS, but they're healthy now after 20 years, they have normal lives, and they have their own families.”

  18. News

    HIV/AIDS Investigators Few and Far Between

    1. Jon Cohen

    The Biomedical Center conducts top-notch studies with foreign collaborators, a surprising rarity in Russia to this day.

    All together now.

    Andrei Kozlov's center works with U.S. investigators on a wide range of studies.

    CREDIT: MALCOLM LINTON

    ST. PETERSBURG, RUSSIA—When it comes to HIV/AIDS research, insiders and outsiders agree that this country, nicknamed the bear, has not lived up to its big and strong moniker. “In the last decade of AIDS research, Russia has not contributed anywhere near her capacity or potential,” says molecular epidemiologist Chris Beyrer of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. In addition to language barriers and other difficulties in accessing information, Beyrer says the country is still reeling from a brain drain that happened when the Soviet Union fell. “It's been very difficult to get the universities back up and running,” says Beyrer, who conducts collaborative HIV/AIDS studies in Russia and trains Russian graduate students. But there are islands of talented investigators. One of them is the Biomedical Center, a privately run and modest institution here. “AIDS science is neglected [in Russia], no question,” says molecular biologist Andrei Kozlov, who runs the center. “This is a shame.”

    Better red.

    IDUs infected by a single HIV variant (red) have near identical isolates—indicated by short branches—in the weeks following transmission.

    CREDIT: ADAPTED FROM ALEXEY E. MASHARSKY ET AL., THE JOURNAL OF INFECTIOUS DISEASES 201 (JUNE 2010)

    Set in a drab, gray-brick building with bars over the windows, the two-story center conducts studies on epidemiology, behavior, molecular characterizations of the virus, and basic vaccine questions. The two dozen investigators have helped clarify the rate of spread of HIV among injecting drug users and documented the transmission from IDUs into the broader population through heterosexual sex. It is the only Russian institution to have joined the U.S. National Institutes of Health's HIV Prevention Trials Network, establishing an IDU cohort for future studies. And several center investigators have trained at Yale University and other top U.S. institutions. “It's a big thing for us to have faith in our collaborators, and the people we're doing virology and social science with there we like enormously,” says Myron Cohen, who directs the Institute for Global Health and Infectious Diseases at the University of North Carolina, Chapel Hill.

    Kozlov, who did a fellowship in Robert Gallo's lab at the U.S. National Cancer Institute before AIDS surfaced, says Russia's difficulties in developing a robust HIV research community stem in part from a long-standing disconnect between medical schools and research institutions. There has also been a leadership vacuum and sharp enmities between different groups. Kozlov, no shrinking violet himself, has had his challenges collaborating, too.

    Difficulties aside, the collaborations have delivered repeatedly. A recently published finding from a study with Cohen has put the group in the midst of a hot debate in HIV vaccine research. An infected person over time develops many viral variants, as HIV constantly mutates. Does a vaccine need to trigger an immune response to stop a swarm of variants, a decidedly tough job? To find out, researchers have hunted for HIVs in newly infected people as close to the moment of transmission as possible and then analyzed genetic variants. It's a tricky business that requires repeatedly taking blood samples from HIV-negative people who are at high risk of becoming infected, but the center and others have managed to do it.

    Studies over the past 2 years have shown convincingly that there is a “bottleneck” with sexual transmission: In about 80% of heterosexuals and 60% of men who have sex with men, only one “founder” virus, for unknown reasons, makes it through the mucosal barriers and establishes an infection. Yet a vaccine that prevents sexual transmission might face steeper challenges if HIV enters by a dirty needle. That's just what a group led by George Shaw at the University of Alabama, Birmingham, found.

    In the June 2010 Journal of Virology, Shaw's team reports that six of 10 IDUs had more than one variant at transmission; one man had 16. Yet the same month, the Biomedical Center team and Cohen published starkly contradictory findings in the Journal of Infectious Disease: In 13 IDUs, nine had a single variant at transmission—roughly the same as heterosexuals. Both studies involve small numbers, and Shaw's group focused on cocaine users who may have injected and shared needles more frequently than did the hero in users in St. Petersburg.

    Whatever the answer, Russian scientists are illuminating a vexing HIV/AIDS issue that has implications far beyond the country's borders. And that, in itself, is something of a roar from what has been a relatively quiet research community.

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